Publications by authors named "Fuqiang Xu"

108 Publications

Identification of metabolic kinetic patterns in different brain regions using metabolomics methods coupled with various discriminant approaches.

J Pharm Biomed Anal 2021 May 16;198:114027. Epub 2021 Mar 16.

Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences-Wuhan National Laboratory for Optoelectronics, 430071, Wuhan, PR China; University of Chinese Academy of Sciences, Beijing, 100049, PR China; Hebei Provincial Key Laboratory of Basic Medicine for Diabetes, 2nd Hospital of Shijiazhuang, Shijiazhuang, Hebei, 050051, PR China. Electronic address:

Metabolomics is widely used as a powerful technique for identifying metabolic patterns and functions of organs and biological systems. Normally, there are multiple groups/targets involved in data processed by discriminant analysis. This is more common in cerebral studies, as there are always several brain regions involved in neuronal studies or brain metabolic dysfunctions. Furthermore, neuronal activity is highly correlated with cerebral energy metabolism, such as oxidation of glucose, especially for glutamatergic (excitatory) and GABAergic (inhibitory) neuronal activities. Thus, regional cerebral energy metabolism recognition is essential for understanding brain functions. In the current study, ten different brain regions were considered for discrimination analysis. The metabolic kinetics were investigated with C enrichments in metabolic products of glucose and measured using the nuclear magnetic spectroscopic method. Multiple discriminative methods were used to construct classification models in order to screen out the best method. After comparing all the applied discriminatory analysis methods, the boost-decision tree method was found to be the best method for classification and every cerebral region exhibited its own metabolic pattern. Finally, the differences in metabolic kinetics among these brain regions were analyzed. We, therefore, concluded that the current technology could also be utilized in other multi-class metabolomics studies and special metabolic kinetic patterns could provide useful information for brain function studies.
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http://dx.doi.org/10.1016/j.jpba.2021.114027DOI Listing
May 2021

Long-term microstructure and cerebral blood flow changes in patients recovered from COVID-19 without neurological manifestations.

J Clin Invest 2021 04;131(8)

Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

BACKGROUNDThe coronavirus disease 2019 (COVID-19) rapidly progressed to a global pandemic. Although some patients totally recover from COVID-19 pneumonia, the disease's long-term effects on the brain still need to be explored.METHODSWe recruited 51 patients with 2 subtypes of COVID-19 (19 mild and 32 severe) with no specific neurological manifestations at the acute stage and no obvious lesions on the conventional MRI 3 months after discharge. Changes in gray matter morphometry, cerebral blood flow (CBF), and white matter (WM) microstructure were investigated using MRI. The relationship between brain imaging measurements and inflammation markers was further analyzed.RESULTSCompared with healthy controls, the decrease in cortical thickness/CBF and the changes in WM microstructure were more severe in patients with severe disease than in those with mild disease, especially in the frontal and limbic systems. Furthermore, changes in brain microstructure, CBF, and tract parameters were significantly correlated (P < 0.05) with the inflammatory markers C-reactive protein, procalcitonin, and interleukin 6.CONCLUSIONIndirect injury related to inflammatory storm may damage the brain, altering cerebral volume, CBF, and WM tracts. COVID-19-related hypoxemia and dysfunction of vascular endothelium may also contribute to neurological changes. The abnormalities in these brain areas need to be monitored during recovery, which could help clinicians understand the potential neurological sequelae of COVID-19.FUNDINGNatural Science Foundation of China.
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http://dx.doi.org/10.1172/JCI147329DOI Listing
April 2021

Chemical sectioning fluorescence tomography: high-throughput, high-contrast, multicolor, whole-brain imaging at subcellular resolution.

Cell Rep 2021 Feb;34(5):108709

Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology, Wuhan, Hubei 430074, China; MoE Key Laboratory for Biomedical Photonics, School of Engineering Sciences, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China. Electronic address:

A thorough neuroanatomical study of the brain architecture is crucial for understanding its cellular compositions, connections, and working mechanisms. However, the fine- and multiscale features of neuron structures make it challenging for microscopic imaging, as it requires high contrast and high throughput simultaneously. Here, we propose chemical sectioning fluorescence tomography (CSFT) to solve this problem. By chemically switching OFF/ON the fluorescent state of the labeled proteins (FPs), we light only the top layer as thin as submicron for imaging without background interference. Combined with the wide-field fluorescence micro-optical sectioning tomography (fMOST) system, we have shown multicolor CSFT imaging. We also demonstrate mouse whole-brain imaging at the subcellular resolution, as well as the power for quantitative acquisition of synaptic-connection-related pyramidal dendritic spines and axon boutons on the brain-wide scale at the complete single-neuron level. We believe that the CSFT method would greatly facilitate our understanding of the brain-wide neuron networks.
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http://dx.doi.org/10.1016/j.celrep.2021.108709DOI Listing
February 2021

Abnormal neocortex arealization and Sotos-like syndrome-associated behavior in mutant mice.

Sci Adv 2021 Jan 1;7(1). Epub 2021 Jan 1.

College of Life Sciences, Department of Neurosurgery, Zhongnan Hospital of Wuhan University; Frontier Science Center for Immunology and Metabolism, and Medical Research Institute at School of Medicine, Wuhan University, Wuhan 430071, China.

Proper formation of area identities of the cerebral cortex is crucial for cognitive functions and social behaviors of the brain. It remains largely unknown whether epigenetic mechanisms, including histone methylation, regulate cortical arealization. Here, we removed SETD2, the methyltransferase for histone 3 lysine-36 trimethylation (H3K36me3), in the developing dorsal forebrain in mice and showed that is required for proper cortical arealization and the formation of cortico-thalamo-cortical circuits. Moreover, conditional knockout mice exhibit defects in social interaction, motor learning, and spatial memory, reminiscent of patients with the Sotos-like syndrome bearing mutations. SETD2 maintains the expression of clustered protocadherin () genes in an H3K36me3 methyltransferase-dependent manner. Aberrant cortical arealization was recapitulated in heterozygous mice. Together, our study emphasizes epigenetic mechanisms underlying cortical arealization and pathogenesis of the Sotos-like syndrome.
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http://dx.doi.org/10.1126/sciadv.aba1180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775761PMC
January 2021

Popularizing recombinant baculovirus-derived OneBac system for laboratory production of all recombinant adeno-associated virus vector serotypes.

Curr Gene Ther 2021 Jan 17. Epub 2021 Jan 17.

State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Key Laboratory of Magnetic Resonance in Biological Systems, Wuhan Center for Magnetic Resonance, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan, 430071. China.

Background: Recombinant adeno-associated virus (rAAV) has been widely used as an efficient transgenic vector in biomedical research, as well as gene therapy. Serotype-associated transduction efficiency, tissue- or cell-type tropism and immunological profile are major considerations in the various applications of rAAVs. There are increasing needs for different serotypes of rAAV, either naturally isolated or artificially engineered. However, affordable and scalable production of a desired serotype of rAAV remains very difficult, especially for researchers lacking relevant experience.

Objective: On the basis of our previously established single recombinant baculovirus expression vector (BEV)-derived OneBac system, we have optimized the process and expanded the rAAV production range to the full range of serotypes rAAV1-13. Firstly, the AAV Cap gene was optimized to translate by ribosome leaky scanning and the gene of interest (GOI) was cloned into the pFD/Cap-(ITR-GOI)-Rep2 shutte plasmid. Following the classical Bac-to-Bac method, sufficient BEV stock containing all rAAV packaging elements can be quickly obtained. Finally, we can repeatedly scale up production of rAAVs in one week by using a single BEV to infect suspension-cultured Sf9 cells. The rAAV1-13 show relatively high yields ranging from 5×104 to 4×105 VG/cell. More than 1×1015 VG purified rAAVs can be easily obtained from 5 L suspension-cultured Sf9 cells. As expected, rAAV serotypes 1-13 show different potencies for in vitro transduction and celltype tropisms.

Conclusion: In summary, the single BEV-derived OneBac system should prove popular for laboratory scaling-up production of any serotype of rAAV.
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http://dx.doi.org/10.2174/1566523221666210118111657DOI Listing
January 2021

Biphasic exocytosis of herpesvirus from hippocampal neurons and mechanistic implication to membrane fusion.

Cell Discov 2020 Jan 14;6(1). Epub 2020 Jan 14.

California NanoSystems Institute, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095-7227, USA.

Exocytosis is a crucial cellular process involved in the release of neural transmitters or signaling hormones, and disposal of waste or toxic materials. The relationship between structural transition and temporal progression of this process is poorly understood, partly due to lack of adequate tools to resolve such dynamic structures at sufficient resolution in 3D. Exocytosis can be hijacked by some viruses, exemplified by the widely used model α-herpesvirus pseudorabies virus (PRV), which relies on exocytosis for trans-synaptic spread across neurons. Here, we have used cryo electron tomography (cryoET) to capture 199 events of PRV exocytosis from cultured hippocampal neurons. We established cumulative frequency analysis to estimate the relative duration of an exocytosis stage based on the frequency of observed viral particles at that stage. This analysis revealed that PRV exocytosis is biphasic, including a fast, "release phase" driven by fusion proteins and fused membranes, and a slow, "recovery phase" driven by flattening of curved membranes. The biphasic property of exocytosis discovered here appears to be conserved for membrane fusion during viral entry, and our approach of cumulative frequency analysis should have general utility for characterizing other membrane fusion events.
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http://dx.doi.org/10.1038/s41421-019-0134-6DOI Listing
January 2020

Divergent Projection Patterns Revealed by Reconstruction of Individual Neurons in Orbitofrontal Cortex.

Neurosci Bull 2021 Apr 29;37(4):461-477. Epub 2020 Dec 29.

Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology, Wuhan, 430074, China.

The orbitofrontal cortex (OFC) is involved in diverse brain functions via its extensive projections to multiple target regions. There is a growing understanding of the overall outputs of the OFC at the population level, but reports of the projection patterns of individual OFC neurons across different cortical layers remain rare. Here, by combining neuronal sparse and bright labeling with a whole-brain florescence imaging system (fMOST), we obtained an uninterrupted three-dimensional whole-brain dataset and achieved the full morphological reconstruction of 25 OFC pyramidal neurons. We compared the whole-brain projection targets of these individual OFC neurons in different cortical layers as well as in the same cortical layer. We found cortical layer-dependent projections characterized by divergent patterns for information delivery. Our study not only provides a structural basis for understanding the principles of laminar organizations in the OFC, but also provides clues for future functional and behavioral studies on OFC pyramidal neurons.
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http://dx.doi.org/10.1007/s12264-020-00616-1DOI Listing
April 2021

Mutation in ε-Sarcoglycan Induces a Myoclonus-Dystonia Syndrome-Like Movement Disorder in Mice.

Neurosci Bull 2021 Mar 23;37(3):311-322. Epub 2020 Dec 23.

State Key Laboratory of Membrane Biology, College of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Peking University, Beijing, 100871, China.

Myoclonus dystonia syndrome (MDS) is an inherited movement disorder, and most MDS-related mutations have so far been found in the ε-sarcoglycan (SGCE) coding gene. By generating SGCE-knockout (KO) and human 237 C > T mutation knock-in (KI) mice, we showed here that both KO and KI mice exerted typical movement defects similar to those of MDS patients. SGCE promoted filopodia development in vitro and inhibited excitatory synapse formation both in vivo and in vitro. Loss of function of SGCE leading to excessive excitatory synapses that may ultimately contribute to MDS pathology. Indeed, using a zebrafish MDS model, we found that among 1700 screened chemical compounds, Vigabatrin was the most potent in readily reversing MDS symptoms of mouse disease models. Our study strengthens the notion that mutations of SGCE lead to MDS and most likely, SGCE functions to brake synaptogenesis in the CNS.
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http://dx.doi.org/10.1007/s12264-020-00612-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954997PMC
March 2021

Anatomical evidence for the efferent pathway from the hypothalamus to autonomic innervation in the anterior chamber structures of eyes.

Exp Eye Res 2021 01 21;202:108367. Epub 2020 Nov 21.

Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

The autonomic innervation in the anterior chamber (AC) structures might play an efferent role in neural intraocular pressure (IOP) regulation, the center of which is thought to be located in the hypothalamus. In this study, we identified the efferent pathway from the hypothalamus to the autonomic innervation in the AC structures. Retrograde trans-multisynaptic pseudorabies virus (PRV) expressing green or red fluorescent protein, PRV531 and PRV724, was injected into the right and left AC of five rats, respectively; PRV531 was injected into the right AC of another five rats, and a non-trans-synaptic tracer, FAST Dil, was injected into the right AC of five rats as a control. Fluorescence signals in autonomic ganglia,the spinal cord and the central nervous system (CNS) were observed. Seven days after FAST Dil right AC injection, FAST Dil-labeled neurons were observed in the ipsilateral autonomic ganglia, including the superior cervical ganglion, pterygopalatine ganglion, and ciliary ganglion, but not in the CNS. Four and a half days after PRV531 injection into the right AC, PRV531-labeled neurons could be observed in the ipsilateral autonomic ganglia and bilateral hypothalamus nuclei, especially in the suprachiasmatic nucleus, paraventricular nucleus, dorsomedial hypothalamus, perifornical hypothalamus and ventral mammillary nucleus. Fluorescence signals of PRV531 mainly located in the ipsilateral autonomic preganglionic nuclei (Edinger-Westphal nucleus, superior salivatory nucleus and intermediolateral nucleus), but not in sensory trigeminal nuclei. Four and a half days after PRV531 right AC injection and PRV724 left AC injection, PRV531-labeled, PRV724-labeled, and double-labeled neurons could be observed in the above mentioned bilateral hypothalamus nuclei; but few contralateral infection-involving neurons (including double-labeled neurons) could be detected in the autonomic preganglionic nuclei. Our results indicate that there exist a both crossed and uncrossed hypothalamo-pre-parasympathetic and -pre-sympathetic tracts in the efferent pathways between the bilateral hypothalamic nuclei and the autonomic innervation of the bilateral AC.
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http://dx.doi.org/10.1016/j.exer.2020.108367DOI Listing
January 2021

Qualitative and Quantitative Analysis of Regional Cerebral Free Fatty Acids in Rats Using the Stable Isotope Labeling Liquid Chromatography-Mass Spectrometry Method.

Molecules 2020 Nov 6;25(21). Epub 2020 Nov 6.

State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Key Laboratory of Magnetic Resonance in Biological Systems, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan 430071, China.

Free fatty acids serve as important bioactive molecules in the brain. They are involved in message transfer in the brain. There are many reports available in the literature regarding the role of cerebral fatty acids in message transfer; however, most of the studies are mainly focused on limited fatty acid species or only a few specific brain regions. To understand the relationship between cerebral functions and free fatty acids, it is necessary to investigate the distribution of the free fatty acids among different regions in the whole brain. In this study, free fatty acids were extracted from different brain regions and analyzed qualitatively and quantitatively using the stable isotopic labeling liquid chromatography-mass spectrometry approach. In total, 1008 potential free fatty acids were detected in the whole brain out of which 38 were found to be commonly present in all brain regions. Among different brain regions, the highest and the smallest amounts of potential free fatty acids were detected in the olfactory bulb and cerebellum, respectively. From a statistical point of view, 4-methyl-2-oxovaleric acid, -11, 14-eicosadienoic acid, tridecanoic acid, myristic acid, nonadecanoic acid, and arachidic acid were found to significantly vary among the four different brain regions (olfactory bulb, occipital lobe, hippocampus, and cerebellum). The variation in the composition of free fatty acids among different brain regions may be very important for investigating the relationship between free fatty acids and functions of cerebral regions.
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http://dx.doi.org/10.3390/molecules25215163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664212PMC
November 2020

A Visual Circuit Related to the Nucleus Reuniens for the Spatial-Memory-Promoting Effects of Light Treatment.

Neuron 2021 01 9;109(2):347-362.e7. Epub 2020 Nov 9.

Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou 510632, China; Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou 510530, China; Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong-Macao Greater Bay Area, Guangzhou 510515, China; Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China. Electronic address:

Light exerts profound effects on cognitive functions across species, including humans. However, the neuronal mechanisms underlying the effects of light on cognitive functions are poorly understood. In this study, we show that long-term exposure to bright-light treatment promotes spatial memory through a di-synaptic visual circuit related to the nucleus reuniens (Re). Specifically, a subset of SMI-32-expressing ON-type retinal ganglion cells (RGCs) innervate CaMKIIα neurons in the thalamic ventral lateral geniculate nucleus and intergeniculate leaflet (vLGN/IGL), which in turn activate CaMKIIα neurons in the Re. Specific activation of vLGN/IGL-projecting RGCs, activation of Re-projecting vLGN/IGL neurons, or activation of postsynaptic Re neurons is sufficient to promote spatial memory. Furthermore, we demonstrate that the spatial-memory-promoting effects of light treatment are dependent on the activation of vLGN/IGL-projecting RGCs, Re-projecting vLGN/IGL neurons, and Re neurons. Our results reveal a dedicated subcortical visual circuit that mediates the spatial-memory-promoting effects of light treatment.
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http://dx.doi.org/10.1016/j.neuron.2020.10.023DOI Listing
January 2021

Sex-Related Differential Whole-Brain Input Atlas of Locus Coeruleus Noradrenaline Neurons.

Front Neural Circuits 2020 23;14:53. Epub 2020 Sep 23.

Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics - Huazhong University of Science and Technology (HUST), Wuhan, China.

As the most important organ in our bodies, the brain plays a critical role in deciding sex-related differential features; however, the underlying neural circuitry basis remains unclear. Here, we used a cell-type-specific rabies virus-mediated monosynaptic tracing system to generate a sex differences-related whole-brain input atlas of locus coeruleus noradrenaline (LC-NE) neurons. We developed custom pipelines for brain-wide comparisons of input sources in both sexes with the registration of the whole-brain data set to the Allen Mouse Brain Reference Atlas. Among 257 distinct anatomical regions, we demonstrated the differential proportions of inputs to LC-NE neurons in male and female mice at different levels. Locus coeruleus noradrenaline neurons of two sexes showed general similarity in the input patterns, but with differentiated input proportions quantitatively from major brain regions and diverse sub-regions. For instance, inputs to male LC-NE neurons were found mainly in the cerebrum, interbrain, and cerebellum, whereas inputs to female LC-NE neurons were found in the midbrain and hindbrain. We further found that specific subsets of nuclei nested within sub-regions contributed to overall sex-related differences in the input circuitry. Furthermore, among the totaled 123 anatomical regions with proportion of inputs >0.1%, we also identified 11 sub-regions with significant statistical differences of total inputs between male and female mice, and seven of them also showed such differences in ipsilateral hemispheres. Our study not only provides a structural basis to facilitate our understanding of sex differences at a circuitry level but also provides clues for future sexually differentiated functional studies related to LC-NE neurons.
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http://dx.doi.org/10.3389/fncir.2020.00053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541090PMC
September 2020

AAV9-Retro mediates efficient transduction with axon terminal absorption and blood-brain barrier transportation.

Mol Brain 2020 10 14;13(1):138. Epub 2020 Oct 14.

Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, 430074, China.

Recombinant adeno-associated viruses (rAAVs), particularly those that permit efficient gene transfer to neurons from axonal terminals or across the blood-brain barrier, are useful vehicles for structural and functional studies of the neural circuit and for the treatment of many gene-deficient brain diseases that need to compensate for the correct genes in every cell in the whole brain. However, AAVs with these two advantages have not been reported. Here, we describe a new capsid engineering method, which exploits the combination of different capsids and aims to yield a capsid that can provide more alternative routes of administration that are more suitable for the wide-scale transduction of the central nervous system (CNS). A new AAV variant, AAV9-Retro, was developed by inserting the 10-mer peptide fragment from AAV2-Retro into the capsid of AAV9, and the biodistribution properties were evaluated in mice. By intracranial and intravenous injection in the mice, we found that AAV9-Retro can retrogradely infect projection neurons with an efficiency comparable to that of AAV2-Retro and retains the characteristic of AAV9, which can be transported across the nervous system. Our strategy provides a new tool for the manipulation of neural circuits and future preclinical and clinical treatment of some neurological and neurodegenerative disorders.
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http://dx.doi.org/10.1186/s13041-020-00679-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556953PMC
October 2020

Neuronal mechanisms of adenosine A receptors in the loss of consciousness induced by propofol general anesthesia with functional magnetic resonance imaging.

J Neurochem 2021 Mar 6;156(6):1020-1032. Epub 2020 Sep 6.

Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, P.R. China.

Propofol is the most common intravenous anesthetic agent for induction and maintenance of anesthesia, and has been used clinically for more than 30 years. However, the mechanism by which propofol induces loss of consciousness (LOC) remains largely unknown. The adenosine A receptor (A R) has been extensively proven to have an effect on physiological sleep. It is, therefore, important to investigate the role of A R in the induction of LOC using propofol. In the present study, the administration of the highly selective A R agonist (CGS21680) and antagonist (SCH58261) was utilized to investigate the function of A R under general anesthesia induced by propofol by means of animal behavior studies, resting-state magnetic resonance imaging and c-Fos immunofluorescence staining approaches. Our results show that CGS21680 significantly prolonged the duration of LOC induced by propofol, increased the c-Fos expression in nucleus accumbens (NAc) and suppressed the functional connectivity of NAc-dorsal raphe nucleus (DR) and NAc-cingulate cortex (CG). However, SCH58261 significantly shortened the duration of LOC induced by propofol, decreased the c-Fos expression in NAc, increased the c-Fos expression in DR, and elevated the functional connectivity of NAc-DR and NAc-CG. Collectively, our findings demonstrate the important roles played by A R in the LOC induced by propofol and suggest that the neural circuit between NAc-DR maybe controlled by A R in the mechanism of anesthesia induced by propofol.
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http://dx.doi.org/10.1111/jnc.15146DOI Listing
March 2021

Investigation of robust visual reaction and functional connectivity in the rat brain induced by rocuronium bromide with functional MRI.

Am J Transl Res 2020 15;12(6):2396-2408. Epub 2020 Jun 15.

Center of Brain Science, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Key Laboratory of Magnetic Resonance in Biological Systems, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences Wuhan 430071, Hubei, P. R. China.

Functional magnetic resonance imaging (fMRI) has been used extensively to understand the brain function of a wide range of neurological and psychiatric disorders. When applied to animal studies, anesthesia is always used to reduce the movement of the animal and also reduce the impacts on the results of fMRI. Several awake models have been proposed by applying physical animal movement restrictions. However, restraining devices were designed for individual subject which limits the promotion of fMRI in awake animals. Here, a clinical muscle relaxant rocuronium bromide (RB) was introduced to restrain the animal in fMRI scanning time. The fMRI reactions of the animal induced with RB and the other two commonly used anesthesia protocols were investigated. The results of the fMRI showed that there were increased functional connectivity and well-round visual responses in the RB induced state. Furthermore, significant BOLD signal changes were found in the cortex and thalamus regions when the animal revived from isoflurane, which should be essential to further understand the effects of anesthesia on the brain.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344061PMC
June 2020

Regional cerebral metabolic levels and turnover in awake rats after acute or chronic spinal cord injury.

FASEB J 2020 08 27;34(8):10547-10559. Epub 2020 Jun 27.

Department of Neurosurgery, General Hospital of Ningxia Medical University, Yinchuan, P.R. China.

Spinal cord injury (SCI) is a common cause of disability, which often leads to sensorimotor cortex dysfunction above the spinal injury site. However, the cerebral regional effects on metabolic information after SCI have been little studied. Here, adult Sprague-Dawley rats were divided into acute and chronic treatment groups and sham groups with day-matched periods. The Basso, Beatte, and Bresnahan scores method were utilized to evaluate the changes in behaviors during the recovery of the animals, and the metabolic information was measured with the H-observed/ C-edited NMR method. Total metabolic concentrations in every region were almost similar in both treated groups. However, the metabolic kinetics in most regions in the acute group were significantly altered (P < .05), particularly in the cortical area, thalamus and medulla (P < .01). After long-term recovery, some metabolic kinetics were recovered, especially in the temporal cortex, occipital cortex, and medulla. The metabolic kinetic changes revealed the alteration of metabolism and neurotransmission in different brain regions after SCI, which present evidence for the alternation of brain glucose oxidation. Therefore, this shows the significant influence of SCI on cerebral function and neuroscience research. This study also provides the theoretical basis for clinical therapy after SCI, such as mitochondrial transplantation.
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http://dx.doi.org/10.1096/fj.202000447RDOI Listing
August 2020

A new GABAergic somatostatin projection from the BNST onto accumbal parvalbumin neurons controls anxiety.

Mol Psychiatry 2020 Jun 18. Epub 2020 Jun 18.

Shenzhen Key Lab of Neuropsychiatric Modulation, Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, the Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences (CAS); Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, 518055, China.

The prevailing view is that parvalbumin (PV) interneurons play modulatory roles in emotional response through local medium spiny projection neurons (MSNs). Here, we show that PV activity within the nucleus accumbens shell (sNAc) is required for producing anxiety-like avoidance when mice are under anxiogenic situations. Firing rates of sNAc neurons were negatively correlated to exploration time in open arms (threatening environment). In addition, sNAc neurons exhibited high excitability in a chronic stress mouse model, which generated excessive maladaptive avoidance behavior in an anxiogenic context. We also discovered a novel GABAergic pathway from the anterior dorsal bed nuclei of stria terminalis (adBNST) to sNAc neurons. Optogenetic activation of these afferent terminals in sNAc produced an anxiolytic effect via GABA transmission. Next, we further demonstrated that chronic stressors attenuated the inhibitory synaptic transmission at adBNST → sNAc synapses, which in turn explains the hyperexcitability of sNAc PV neurons on stressed models. Therefore, activation of these GABAergic afferents in sNAc rescued the excessive avoidance behavior related to an anxious state. Finally, we identified that the majority GABAergic input neurons, which innervate sNAc cells, were expressing somatostatin (SOM), and also revealed that coordination between SOM- and PV- cells functioning in the BNST → NAc circuit has an inhibitory influence on anxiety-like responses. Our findings provide a potentially neurobiological basis for therapeutic interventions in pathological anxiety.
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http://dx.doi.org/10.1038/s41380-020-0816-3DOI Listing
June 2020

Functions of lactate in the brain of rat with intracerebral hemorrhage evaluated with MRI/MRS and in vitro approaches.

CNS Neurosci Ther 2020 Jun 2. Epub 2020 Jun 2.

State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Key Laboratory of Magnetic Resonance in Biological Systems, Wuhan Center for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan, China.

Introduction: Lactate accumulation in the brain is caused by the anaerobic metabolism induced by ischemic damages, which always accompanies intracerebral hemorrhages (ICH). Our former findings showed that microglia's movement was always directly toward hemorrhagic center with the highest lactate concentration, and penumbra area has the largest density of compactly arrayed microglia. However, the relationship between microglia and lactate concentration has not been well documented.

Methods: Cerebral hemorrhage model was successfully achieved by injecting collagenase VII (causing stabile localized bleeding) in CPu (striatum) of SD rats. Emodin was used as a potential therapeutic for ICH. The function of the lactate was examined with in vitro culture studies. Then, the effect of lactate on the proliferation, cell survival, migration, and phagocytosis property of microglia was investigated by in vitro culture studies.

Results: Lactate accumulation was observed with in vivo MRS method, and its concentration was monitored during the recovery of ICH and treatment of emodin. Lactate concentration significantly increased in the core and penumbra regions of hemorrhagic foci, and it decreased after the treatment of emodin. The in vitro culture study was verified that lactate was beneficial for the proliferation, cell survival, migration, and phagocytosis property of the microglia.

Conclusion: Results from in vitro verification study, investigations from the recovery of ICH, and treatment of emodin verify that lactate plays an important role during the recovery of ICH. This could provide a novel therapeutic approach for ICH.
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http://dx.doi.org/10.1111/cns.13399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539841PMC
June 2020

imaging of Zika virus reveals dynamics of viral invasion in immune-sheltered tissues and vertical propagation during pregnancy.

Theranostics 2020 16;10(14):6430-6447. Epub 2020 May 16.

CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.

: Zika virus (ZIKV) is a pathogenic virus known to cause a wide range of congenital abnormalities, including microcephaly, Guillain-Barre syndrome, meningoencephalitis, and other neurological complications, in humans. This study investigated the noninvasive detection of ZIKV infection , which is necessary for elucidating the virus's mechanisms of viral replication and pathogenesis, as well as to accelerate the development of anti-ZIKV therapeutic strategies. : In this study, a recombinant ZIKV harbouring Nluc gene (ZIKV-Nluc) was designed, recovered, and purified. The levels of bioluminescence were directly correlated with viral loads and . The dynamics of ZIKV infection in A129 (interferon (IFN)-α/β receptor deficient), AG6 (IFN-α/β and IFN-γ receptor deficient), and C57BL/6 mice were characterized. Pregnant dams were infected with ZIKV-Nluc at E10 via intra footpad injection. Then, the pooled immune sera (anti-ZIKV neutralizing antibodies) #22-1 in ZIKV-Nluc virus-infected mice were visualized. : ZIKV-Nluc showed a high genetic stability and replicated well in cells with similar properties to the wild-type ZIKV (ZIKVwt). Striking bioluminescence signals were consistently observed in animal organs, including spleen, intestine, testis, uterus/ovary, and kidney. The ileocecal junction was found to be the crucial visceral target. Infection of pregnant dams with ZIKV-Nluc showed that ZIKV was capable of crossing the maternal-fetal barrier to infect the fetuses via vertical transmission. Furthermore, it was visualized that treatment with the pooled immune sera was found to greatly restrict the spread of the ZIKV-Nluc virus in mice. : This study is the first to report the real-time noninvasive tracking of the progression of ZIKV invading immune-sheltered tissues and propagating vertically during pregnancy. The results demonstrate that ZIKV-Nluc represents a powerful tool for the study of the replication, dissemination, pathogenesis, and treatment of ZIKV and .
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http://dx.doi.org/10.7150/thno.43177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255039PMC
May 2020

Brain control of humoral immune responses amenable to behavioural modulation.

Nature 2020 05 29;581(7807):204-208. Epub 2020 Apr 29.

Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China.

It has been speculated that brain activities might directly control adaptive immune responses in lymphoid organs, although there is little evidence for this. Here we show that splenic denervation in mice specifically compromises the formation of plasma cells during a T cell-dependent but not T cell-independent immune response. Splenic nerve activity enhances plasma cell production in a manner that requires B-cell responsiveness to acetylcholine mediated by the α9 nicotinic receptor, and T cells that express choline acetyl transferase probably act as a relay between the noradrenergic nerve and acetylcholine-responding B cells. We show that neurons in the central nucleus of the amygdala (CeA) and the paraventricular nucleus (PVN) that express corticotropin-releasing hormone (CRH) are connected to the splenic nerve; ablation or pharmacogenetic inhibition of these neurons reduces plasma cell formation, whereas pharmacogenetic activation of these neurons increases plasma cell abundance after immunization. In a newly developed behaviour regimen, mice are made to stand on an elevated platform, leading to activation of CeA and PVN CRH neurons and increased plasma cell formation. In immunized mice, the elevated platform regimen induces an increase in antigen-specific IgG antibodies in a manner that depends on CRH neurons in the CeA and PVN, an intact splenic nerve, and B cell expression of the α9 acetylcholine receptor. By identifying a specific brain-spleen neural connection that autonomically enhances humoral responses and demonstrating immune stimulation by a bodily behaviour, our study reveals brain control of adaptive immunity and suggests the possibility to enhance immunocompetency by behavioural intervention.
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http://dx.doi.org/10.1038/s41586-020-2235-7DOI Listing
May 2020

Correction to: Regional Metabolic Patterns of Abnormal Postoperative Behavioral Performance in Aged Mice Assessed by H-NMR Dynamic Mapping Method.

Neurosci Bull 2020 May;36(5):565-566

Department of Anesthesiology, Peking University Third Hospital, Beijing, 100191, China.

The original version of this article unfortunately contained some mistakes.
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http://dx.doi.org/10.1007/s12264-020-00488-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186279PMC
May 2020

A mutant vesicular stomatitis virus with reduced cytotoxicity and enhanced anterograde trans-synaptic efficiency.

Mol Brain 2020 03 20;13(1):45. Epub 2020 Mar 20.

Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, 430074, China.

Understanding the connecting structure of brain network is the basis to reveal the principle of the brain function and elucidate the mechanism of brain diseases. Trans-synaptic tracing with neurotropic viruses has become one of the most effective technologies to dissect the neural circuits. Although the retrograde trans-synaptic tracing for analyzing the input neural networks with recombinant rabies and pseudorabies virus has been broadly applied in neuroscience, viral tools for analyzing the output neural networks are still lacking. The recombinant vesicular stomatitis virus (VSV) has been used for the mapping of synaptic outputs. However, several drawbacks, including high neurotoxicity and rapid lethality in experimental animals, hinder its application in long-term studies of the structure and function of neural networks. To overcome these limitations, we generated a recombinant VSV with replication-related N gene mutation, VSV-N, and examined its cytotoxicity and efficiency of trans-synaptic spreading. We found that by comparison with the wild-type tracer of VSV, the N mutation endowed the virus lower rate of propagation and cytotoxicity in vitro, as well as significantly reduced neural inflammatory responses in vivo and much longer animal survival when it was injected into the nucleus of the mice brain. Besides, the spreading of the attenuated VSV was delayed when injected into the VTA. Importantly, with the reduced toxicity and extended animal survival, the number of brain regions that was trans-synaptically labeled by the mutant VSV was more than that of the wild-type VSV. These results indicated that the VSV-N, could be a promising anterograde tracer that enables researchers to explore more downstream connections of a given brain region, and observe the anatomical structure and the function of the downstream circuits over a longer time window. Our work could provide an improved tool for structural and functional studies of neurocircuit.
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http://dx.doi.org/10.1186/s13041-020-00588-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7085170PMC
March 2020

Cell-Type-Specific Whole-Brain Direct Inputs to the Anterior and Posterior Piriform Cortex.

Front Neural Circuits 2020 7;14. Epub 2020 Feb 7.

Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, China.

The piriform cortex (PC) is a key brain area involved in both processing and coding of olfactory information. It is implicated in various brain disorders, such as epilepsy, Alzheimer's disease, and autism. The PC consists of the anterior (APC) and posterior (PPC) parts, which are different anatomically and functionally. However, the direct input networks to specific neuronal populations within the APC and PPC remain poorly understood. Here, we mapped the whole-brain direct inputs to the two major neuronal populations, the excitatory glutamatergic principal neurons and inhibitory γ-aminobutyric acid (GABA)-ergic interneurons within the APC and PPC using the rabies virus (RV)-mediated retrograde trans-synaptic tracing system. We found that for both types of neurons, APC and PPC share some similarities in input networks, with dominant inputs originating from the olfactory region (OLF), followed by the cortical subplate (CTXsp), isocortex, cerebral nuclei (CNU), hippocampal formation (HPF) and interbrain (IB), whereas the midbrain (MB) and hindbrain (HB) were rarely labeled. However, APC and PPC also show distinct features in their input distribution patterns. For both types of neurons, the input proportion from the OLF to the APC was higher than that to the PPC; while the PPC received higher proportions of inputs from the HPF and CNU than the APC did. Overall, our results revealed the direct input networks of both excitatory and inhibitory neuronal populations of different PC subareas, providing a structural basis to analyze the diverse PC functions.
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http://dx.doi.org/10.3389/fncir.2020.00004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019026PMC
February 2020

Visuoauditory Associative Memory Established with Cholecystokinin Under Anesthesia Is Retrieved in Behavioral Contexts.

J Neurosci 2020 03 24;40(10):2025-2037. Epub 2020 Jan 24.

Departments of Biomedical Sciences, Biology, and Chemistry, City University of Hong Kong, Hong Kong, China,

Plastic change in neuronal connectivity is the foundation of memory encoding. It is not clear whether the changes during anesthesia can alter subsequent behavior. Here, we demonstrated that in male rodents under anesthesia, a visual stimulus (VS) was associated with electrical stimulation of the auditory cortex or natural auditory stimulus in the presence of cholecystokinin (CCK), which guided the animals' behavior in a two-choice auditory task. Auditory neurons became responsive to the VS after the pairings. Moreover, high-frequency stimulation of axon terminals of entorhinal CCK neurons in the auditory cortex enabled LTP of the visual response in the auditory cortex. Such pairing during anesthesia also generated VS-induced freezing in an auditory fear conditioning task. Finally, we verified that direct inputs from the entorhinal CCK neurons and the visual cortex enabled the above neural plasticity in the auditory cortex. Our findings suggest that CCK-enabled visuoauditory association during anesthesia can be translated to the subsequent behavior action. Our study provides strong evidence for the hypothesis that cholecystokinin plays an essential role in the formation of cross-modal associative memory. Moreover, we demonstrated that an entorhinal-neocortical circuit underlies such neural plasticity, which will be helpful to understand the mechanisms of memory formation and retrieval in the brain.
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http://dx.doi.org/10.1523/JNEUROSCI.1673-19.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055132PMC
March 2020

Biphasic exocytosis of herpesvirus from hippocampal neurons and mechanistic implication to membrane fusion.

Cell Discov 2020 14;6. Epub 2020 Jan 14.

2California NanoSystems Institute, University of California, Los Angeles (UCLA), Los Angeles, CA 90095-7227 USA.

Exocytosis is a crucial cellular process involved in the release of neural transmitters or signaling hormones, and disposal of waste or toxic materials. The relationship between structural transition and temporal progression of this process is poorly understood, partly due to lack of adequate tools to resolve such dynamic structures at sufficient resolution in 3D. Exocytosis can be hijacked by some viruses, exemplified by the widely used model α-herpesvirus pseudorabies virus (PRV), which relies on exocytosis for trans-synaptic spread across neurons. Here, we have used cryo electron tomography (cryoET) to capture 199 events of PRV exocytosis from cultured hippocampal neurons. We established cumulative frequency analysis to estimate the relative duration of an exocytosis stage based on the frequency of observed viral particles at that stage. This analysis revealed that PRV exocytosis is biphasic, including a fast, "release phase" driven by fusion proteins and fused membranes, and a slow, "recovery phase" driven by flattening of curved membranes. The biphasic property of exocytosis discovered here appears to be conserved for membrane fusion during viral entry, and our approach of cumulative frequency analysis should have general utility for characterizing other membrane fusion events.
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http://dx.doi.org/10.1038/s41421-019-0134-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957672PMC
January 2020

Effects of microbial inoculants on the fermentation characteristics and microbial communities of sweet sorghum bagasse silage.

Sci Rep 2020 01 21;10(1):837. Epub 2020 Jan 21.

Institute of Modern Physics, Chinese Academy of Sciences, 509 Nanchang Rd., Lanzhou, Gansu, 730000, P.R. China.

Sweet sorghum bagasse (SSB) is a promising raw material for silage fermentation due to its high residual nutritive, but the efficient fermentation strategy of SSB has not been reported yet. This study evaluated the effects of microbial inoculant on the fermentation quality, chemical composition and microbial community of SSB silage. The silage inoculated with isolated lactic acid bacteria (LpE) achieved better fermentation than that of commercial inoculant A, B (CIA, CIB) and untreatment, including low pH value, high levels of lactic acid and water soluble carbohydrates (WSC) content, which demonstrated that the LpE inoculant could contribute to the preservation of nutrition and the manipulation of fermentation process of SSB. In addition, the results of microbial community analysis indicated that the LpE inoculant significantly changed the composition and diversity of bacteria in SSB silage. After ensiling, the LpE inoculated silage were dominated by Lactobacillus(95.71%), Weissella(0.19%). These results were of great guiding significance aiming for high-quality silage production using SSB materials on the basis of target-based regulation methods.
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http://dx.doi.org/10.1038/s41598-020-57628-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6972861PMC
January 2020

High-brightness anterograde transneuronal HSV1 H129 tracer modified using a Trojan horse-like strategy.

Mol Brain 2020 01 13;13(1). Epub 2020 Jan 13.

Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, 430074, China.

Neurotropic viral transsynaptic tracing is an increasingly powerful technique for dissecting the structure and function of neural circuits. Herpes simplex virus type 1 strain H129 has been widely used as an anterograde tracer. However, HSV tracers still have several shortcomings, including high toxicity, low sensitivity and non-specific retrograde labeling. Here, we aimed to construct high-brightness HSV anterograde tracers by increasing the expression of exogenous genes carried by H129 viruses. Using a Trojan horse-like strategy, a HSV/AAV (adeno-associated virus) chimaera termed H8 was generated to enhance the expression of a fluorescent marker. In vitro and in vivo assays showed that the exogenous gene was efficiently replicated and amplified by the synergism of the HSV vector and introduced AAV replication system. H8 reporting fluorescence was brighter than that of currently available H129 tracers, and H8 could be used for fast and effective anterograde tracing without additional immunostaining. These results indicated that foreign gene expression in HSV tracers could be enhanced by integrating HSV with AAV replication system. This approach may be useful as a general enhanced expression strategy for HSV-based tracing tools or gene delivery vectors.
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http://dx.doi.org/10.1186/s13041-020-0544-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6958791PMC
January 2020

Pretreatment of sweet sorghum straw and its enzymatic digestion: insight into the structural changes and visualization of hydrolysis process.

Biotechnol Biofuels 2019 23;12:276. Epub 2019 Nov 23.

1Institute of Modern Physics, Chinese Academy of Sciences, 509 Nanchang Rd., Lanzhou, 730000 Gansu People's Republic of China.

Background: The efficient utilization of lignocellulosic biomass for biofuel production has received increasing attention. Previous studies have investigated the pretreatment process of biomass, but the detailed enzymatic hydrolysis process of pretreated biomass remains largely unclear. Thus, this study investigated the pretreatment efficiency of dilute alkali, acid, hydrogen peroxide and its ultimate effects on enzymatic hydrolysis. Furthermore, to better understand the enzymatic digestion process of alkali-pretreated sweet sorghum straw (SSS), multimodal microscopy techniques were used to visualize the enzymatic hydrolysis process.

Result: After pretreatment with alkali, an enzymatic hydrolysis efficiency of 86.44% was obtained, which increased by 99.54% compared to the untreated straw (43.23%). The FTIR, XRD and SEM characterization revealed a sequence of microstructural changes occurring in plant cell walls after pretreatment, including the destruction of lignin-polysaccharide interactions, the increase of porosity and crystallinity, and reduction of recalcitrance. During the course of hydrolysis, the cellulase dissolved the cell walls in the same manner and the digestion firstly occurred from the middle of cell walls and then toward the cell wall corners. The CLSM coupled with fluorescent labeling demonstrated that the sclerenchyma cells and vascular bundles in natural SSS were highly lignified, which caused the nonproductive bindings of cellulase on lignin. However, the efficient delignification significantly increased the accessibility and digestibility of cellulase to biomass, thereby improving the saccharification efficiency.

Conclusion: This work will be helpful in investigating the biomass pretreatment and its structural characterization. In addition, the visualization results of the enzymatic hydrolysis process of pretreated lignocellulose could be used for guidance to explore the lignocellulosic biomass processing and large-scale biofuel production.
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http://dx.doi.org/10.1186/s13068-019-1613-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6874820PMC
November 2019

Elevated glutamate, glutamine and GABA levels and reduced taurine level in a schizophrenia model using an in vitro proton nuclear magnetic resonance method.

Am J Transl Res 2019 15;11(9):5919-5931. Epub 2019 Sep 15.

Department of Psychiatry, The First Affiliated Hospital of China Medical University Shenyang, Liaoning, P. R. China.

Accumulating evidence suggests that brain metabolic changes may be associated with the pathophysiology of schizophrenia. Both and studies have found glutamatergic and GABAergic abnormalities in different brain regions of individuals with schizophrenia. We report a longitudinal behavioral study in a methylazoxymethanol acetate (MAM) rat model of schizophrenia at three different age periods: prepuberty, late-puberty and early-adulthood. MAM-treated rats showed stable hypolocomotive activity, anxiety and cognitive deficits from late-puberty to early-adulthood. Therefore we detected the metabolites changes of adult MAM-treated rats using an proton nuclear magnetic resonance (H-NMR) method. In the MAM-treated rats, glutamate was increased in the thalamus and hypothalamus, glutamine was increased in the hippocampus and GABA was increased in the hippocampus and prefrontal cortex, while taurine showed a decrease in the striatum, temporal cortex and parietal cortex. These abnormalities may be helped further understanding the pathophysiology of schizophrenia.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789232PMC
September 2019

Glutamatergic Neurons in the Piriform Cortex Influence the Activity of D1- and D2-Type Receptor-Expressing Olfactory Tubercle Neurons.

J Neurosci 2019 11 18;39(48):9546-9559. Epub 2019 Oct 18.

Department of Pharmacology and Therapeutics, University of Florida, Gainesville, Florida 32610,

Sensory cortices process stimuli in manners essential for perception. Very little is known regarding interactions between olfactory cortices. The piriform "primary" olfactory cortex, especially its anterior division (aPCX), extends dense association fibers into the ventral striatum's olfactory tubercle (OT), yet whether this corticostriatal pathway is capable of shaping OT activity, including odor-evoked activity, is unknown. Further unresolved is the synaptic circuitry and the spatial localization of OT-innervating PCX neurons. Here we build upon standing literature to provide some answers to these questions through studies in mice of both sexes. First, we recorded the activity of OT neurons in awake mice while optically stimulating principal neurons in the aPCX and/or their association fibers in the OT while the mice were delivered odors. This uncovered evidence that PCX input indeed influences OT unit activity. We then used patch-clamp recordings and viral tracing to determine the connectivity of aPCX neurons upon OT neurons expressing dopamine receptor types D1 or D2, two prominent cell populations in the OT. These investigations uncovered that both populations of neurons receive monosynaptic inputs from aPCX glutamatergic neurons. Interestingly, this input originates largely from the ventrocaudal aPCX. These results shed light on some of the basic physiological properties of this pathway and the cell-types involved and provide a foundation for future studies to identify, among other things, whether this pathway has implications for perception. Sensory cortices interact to process stimuli in manners considered essential for perception. Very little is known regarding interactions between olfactory cortices. The present study sheds light on some of the basic physiological properties of a particular intercortical pathway in the olfactory system and provides a foundation for future studies to identify, among other things, whether this pathway has implications for perception.
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http://dx.doi.org/10.1523/JNEUROSCI.1444-19.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880455PMC
November 2019