Publications by authors named "Xiao-Xin Yan"

72 Publications

MFGE8 mitigates brain injury in a rat model of SAH by maintaining vascular endothelial integrity via TIGβ5/PI3K/CXCL12 signaling.

Exp Brain Res 2021 May 15. Epub 2021 May 15.

Department of Neurosurgery, The Fifth Affiliated Hospital of Sun Yat-sen University, No. 52 Meihuadong Road, Zhuhai, 519000, Guangdong, China.

Leaked blood components, injured endothelial cells, local inflammatory response and vasospasm may converge to promote microthrombosis following subarachnoid hemorrhage (SAH). Previously, we showed that the milk fat globule-epidermal growth factor 8 (MFGE8) can mitigate SAH-induced microthrombosis. This present study was aimed to explore the molecular pathway participated in MFGE8-dependent protection on vascular endothelium. Immunofluorescence, immunoblot and behavioral tests were used to determine the molecular partner and signaling pathway mediating the effect of MFGE8 in vascular endothelium in rats with experimental SAH and controls, together with the applications of RNA silencing and pharmacological intervention methods. Relative to control, recombinant human MFGE8 (rhMFGE8) treatment increased 5-bromo-2'-deoxyuridine (BrdU) labeled new endothelial cells, reduced TUNUL-positive endothelial cells and elevated the expression of phosphatidylinositol 3-kinase (PI3K) and chemokine (C-X-C motif) ligand 12 (CXCL12), in the brains of SAH rats. These effects were reversed by MFGE8 RNA silencing, as well as following cilengitide and wortmannin intervention. These results suggest that MFGE8 promotes endothelial regeneration and mitigates endothelial DNA damage through the activation of the TIGβ5/PI3K/CXCL12 signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00221-021-06111-xDOI Listing
May 2021

Association of SHANK Family with Neuropsychiatric Disorders: An Update on Genetic and Animal Model Discoveries.

Cell Mol Neurobiol 2021 Feb 17. Epub 2021 Feb 17.

Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.

The Shank family proteins are enriched at the postsynaptic density (PSD) of excitatory glutamatergic synapses. They serve as synaptic scaffolding proteins and appear to play a critical role in the formation, maintenance and functioning of synapse. Increasing evidence from genetic association and animal model studies indicates a connection of SHANK genes defects with the development of neuropsychiatric disorders. In this review, we first update the current understanding of the SHANK family genes and their encoded protein products. We then denote the literature relating their alterations to the risk of neuropsychiatric diseases. We further review evidence from animal models that provided molecular insights into the biological as well as pathogenic roles of Shank proteins in synapses, and the potential relationship to the development of abnormal neurobehavioral phenotypes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10571-021-01054-xDOI Listing
February 2021

Early Dendritic Dystrophy in Human Brains With Primary Age-Related Tauopathy.

Front Aging Neurosci 2020 7;12:596894. Epub 2020 Dec 7.

Department of Anatomy and Neurobiology, Xiangya School of Medicine, Central South University, Changsha, China.

Dystrophic neurites (DNs) are found in many neurological conditions such as traumatic brain injury and age-related neurodegenerative diseases. In Alzheimer's disease (AD) specifically, senile plaques containing silver-stained DNs were already described in the original literature defining this disease. These DNs could be both axonal and dendritic in origin, while axonal dystrophy relative to plaque formation has been more extensively studied. Here, we demonstrate an early occurrence of dendritic dystrophy in the hippocampal CA1 and subicular regions in human brains ( = 23) with primary age-related tauopathy (PART), with neurofibrillary tangle (NFT) burden ranging from Braak stages I to III in the absence of cerebral β-amyloid (Aβ) deposition. In Bielschowsky's silver stain, segmented fusiform swellings on the apical dendrites of hippocampal and subicular pyramidal neurons were observed in all the cases, primarily over the stratum radiatum (s.r.). The numbers of silver-stained neuronal somata and dendritic swellings counted over CA1 to subiculum were positively correlated among the cases. Swollen dendritic processes were also detected in sections immunolabeled for phosphorylated tau (pTau) and sortilin. In aged and AD brains with both Aβ and pTau pathologies, silver- and immunolabeled dystrophic-like dendritic profiles occurred around and within individual neuritic plaques. These findings implicate that dendritic dystrophy can occur among hippocampal pyramidal neurons in human brains with PART. Therefore, as with the case of axonal dystrophy reported in literature, dendritic dystrophy can develop prior to Alzheimer-type plaque and tangle formation in the human brain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnagi.2020.596894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7750631PMC
December 2020

Extracellular Sortilin Proteopathy Relative to β-Amyloid and Tau in Aged and Alzheimer's Disease Human Brains.

Front Aging Neurosci 2020 12;12:93. Epub 2020 May 12.

Department of Anatomy and Neurobiology, Xiangya School of Medicine, Central South University, Changsha, China.

Amyloid plaques and neurofibrillary tangles (NFTs) are hallmark lesions of Alzheimer's disease (AD) related to β-amyloid (Aβ) deposition and intraneuronal phosphorylated tau (pTau) accumulation. tilin C-terminal gments (shortened as "sorfra") can deposit as senile plaque-like lesions within AD brains. The course and pattern of sorfra plaque formation relative to Aβ and pTau pathogenesis remain unknown. In the present study, cerebral and subcortical sections in postmortem human brains ( = 46) from aged and AD subjects were stained using multiple markers (6E10, β-secretase 1, pTau, and sortilin antibodies, as well as Bielschowsky silver stain). The course and pattern of sorfra plaque formation relative to Thal Aβ and Braak NFT pathogenic stages were determined. Sorfra plaques occurred in the temporal, inferior frontal and occipital neocortices in cases with Thal 1 and Braak III stages. They were also found additionally in the hippocampal formation, amygdala, and associative neocortex in cases with Thal 2-4 and Braak IV-V. Lastly, they were also found in the primary motor, somatosensory, and visual cortices in cases with Thal 4-5 and Braak VI. Unlike Aβ and pTau pathologies, sorfra plaques did not occur in subcortical structures in cases with Aβ/pTau lesions in Thal 3-5/Braak IV-VI stages. We establish here that sorfra plaques are essentially a cerebral proteopathy. We believe that the development of sorfra plaques in both cortical and hippocampal regions proceeds in a typical spatiotemporal pattern, and the stages of cerebral sorfra plaque formation partially overlap with that of Aβ and pTau pathologies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnagi.2020.00093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236809PMC
May 2020

Who is willing to donate their bodies in China? Perceptions, attitudes and influencing factors among citizens of Changsha.

Ann Anat 2020 May 13;229:151483. Epub 2020 Feb 13.

Department of Human Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha 410013, Hunan, China. Electronic address:

Body donation has far-reaching significance for modern medical research and education. However, body donation in China lags far behind the demand. To assess the perception and attitude toward body donation, a survey of 2535 community residents was conducted in Changsha. The result showed that 89.5% of the respondents have heard about body donation through different sources, such as public media, medical college, and hospital. However, 61.8% of the respondents have limited knowledge of these body donation programs. The majority of respondents believed that body donation would contribute to researches in neuroanatomy, tumor biology, and ophthalmology, as well as anatomical education for medical students, and surgical training for clinicians/surgeons. Regarding the public's willingness to donate, 27.5% of respondents expressed a clear willingness. Further analysis revealed that people aged above 60 are less willing to donate. Compared with people having Confucianism funeral belief, those without the belief were 9.8 times more willing to donate. Furthermore, it was shown that respondents who had a good understanding of body donation were more willing to donate their bodies. Moreover, people thought body donation was beneficial to medical research and education were almost 10 times more willing to donate compared to those who thought it had no benefit. To promote body donation in China, greater efforts need to be made in promoting body donor programs and so increasing the public's perception toward body donation. Moreover, re-assessing and re-interpreting Confucianism beliefs regarding body donation also needs to be considered for future promotion of body donation in China and other East Asian countries.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.aanat.2020.151483DOI Listing
May 2020

Hydrogen Inhalation Attenuates Oxidative Stress Related Endothelial Cells Injury After Subarachnoid Hemorrhage in Rats.

Front Neurosci 2019 21;13:1441. Epub 2020 Jan 21.

Department of Neurosurgery, The Third Xiangya Hospital, Central South University, Changsha, China.

Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular disease with poor clinical outcome. Nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome serves a key role in inflammatory response, which may lead to endothelial cell injury and blood-brain barrier (BBB) disruption. Hydrogen (H) is considered a neuroprotective antioxidant. This study was set out to explore whether hydrogen inhalation protects against SAH induced endothelial cell injury, BBB disruption, microthrombosis and vasospasm in rats. One hundred eighty-two male SD rats were used for the study. SAH was induced by endovascular perforation. H2 at a concentration of 3.3% was inhaled beginning at 0.5 h after SAH for duration of 30, 60 or 120 min, followed by single administration or once daily administration for 3 days. The temporal expression of NLRP3 and ASC in the brain was determined, with the effect of hydrogen inhalation evaluated. In addition, brain water content, oxidative stress markers, inflammasome, apoptotic markers, microthrombosis, and vasospasm were evaluated at 24 or 72 h after SAH. The expression of NLRP3 and ASC were upregulated after SAH associated with elevated expression of MDA, 8-OHdG, 4-HNE, HO-1, TLR4/NF-κB, inflammatory and apoptotic makers. Hydrogen inhalation reduced the expression of these inflammatory and apoptotic makers in the vessels, brain edema, microthrombi formation, and vasospasm in rats with SAH relative to control. Hydrogen inhalation also improved short-term and long-term neurological recovery after SAH. Hydrogen inhalation can ameliorate oxidative stress related endothelial cells injury in the brain and improve neurobehavioral outcomes in rats following SAH. Mechanistically, the above beneficial effects might be related to, at least in part, the inhibition of activation of ROS/NLRP3 axis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnins.2019.01441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6985445PMC
January 2020

Pregnancy Promotes Maternal Hippocampal Neurogenesis in Guinea Pigs.

Neural Plast 2019 11;2019:5765284. Epub 2019 Apr 11.

Department of Anatomy and Neurobiology, Central South University Xiangya School of Medicine, Changsha, Hunan 410013, China.

Adult neurogenesis in the hippocampal dentate gyrus (DG) modulates cognition and behavior in mammals, while motherhood is associated with cognitive and behavioral changes essential for the care of the young. In mice and rats, hippocampal neurogenesis is reported to be reduced or unchanged during pregnancy, with few data available from other species. In guinea pigs, pregnancy lasts ~9 weeks; we set to explore if hippocampal neurogenesis is altered in these animals, relative to gestational stages. Time-pregnant primigravidas (3-5 months old) and age-matched nonpregnant females were examined, with neurogenic potential evaluated via immunolabeling of Ki67, Sp8, doublecortin (DCX), and neuron-specific nuclear antigen (NeuN) combined with bromodeoxyuridine (BrdU) birth-dating. Relative to control, subgranular Ki67, Sp8, and DCX-immunoreactive (+) cells tended to increase from early gestation to postpartum and peaked at the late gestational stage. In BrdU pulse-chasing experiments in nonpregnant females surviving for different time points (2-120 days), BrdU+ cells in the DG colocalized with DCX partially from 2 to 42 days (most frequently at 14-30 days) and with NeuN increasingly from 14 to 120 days. In pregnant females that received BrdU at early, middle, and late gestational stages and survived for 42 days, the density of BrdU+ cells in the DG was mostly high in the late gestational group. The rates of BrdU/DCX and BrdU/NeuN colocalization were similar among these groups and comparable to those among the corresponding control group. Together, the findings suggest that pregnancy promotes maternal hippocampal neurogenesis in guinea pigs, at least among primigravidas.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2019/5765284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6487096PMC
December 2019

Acute restraint stress alters food-foraging behavior in rats: Taking the easier Way while suffered.

Brain Res Bull 2019 07 26;149:184-193. Epub 2019 Apr 26.

Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Tongzipo Road 172, Changsha, Hunan, China. Electronic address:

Stress can influence decision-making in humans from many cognitive perspectives, while the underlying neurobiological mechanism remains incompletely understood. Food-foraging is a rodent behavior involving strategic possessing of nutritional supply in social context; experimental model of this behavior could help explore the effect of stress on decision-making and the brain mechanism thereof. In the present study, the influence of stress on food-foraging behavior was assessed in rats using an open field choosing paradigm wherein food collection (standard food or sweet food) were associated with social competition (with or without a rat in the cage). Acute restraint stress (ARS) was induced by placing the rat in a plastic restrainer for 2 h before food-foraging behavioral tests, with the effect of stress also determined biochemically and immunohistochemically. Restraint stressed rats showed anxiety-like behavior and elevation of serum corticosterone (CORT) and epinephrine (EPI) relative to controls. Both restraint and control animals preferred sugared food. However, the former group tended to forage food from a cage not occupied by a conspecific rat, whereas the control rats preferred to obtain food from the cage with a social competitor. Thus, the total amount of food foraged and eaten are reduced in the restrained rats than in controls. While the restraint animals had normal social interaction with other rats, they displayed enhanced social agonistic behavior. In brain examination, ARS attenuated the increase in immunolabeling and protein levels of c-fos, p-CREB, p-ERK1/2 in the anterior cingulate cortex (ACC) observed in control animals in association with food-foraging. These results indicate that restraint stressed rats tend to forage food by taking the advantage of a less competitive opportunity. Mechanistically, this decision-making alternative appears to be mediated through a neuronal deactivation in the ACC. The current findings provide novel insights into neuronal processing of decision-making behavior under the influence of stress.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.brainresbull.2019.04.021DOI Listing
July 2019

Perceptions and Attitudes toward Brain Donation among the Chinese People.

Anat Sci Educ 2020 Jan 17;13(1):80-90. Epub 2019 May 17.

Xiangya Brain Bank, School of Basic Medical Science, Central South University, Changsha, Hunan, People's Republic of China.

Postmortem human brain donation is crucial to both anatomy education and research. The China Human Brain Banking Consortium was established recently to foster brain donation in China. The purpose of this study was to gain information about the public perception of and attitudes toward brain donation and to identify factors that may impact the willingness to participate in brain donation among the Chinese people. A specifically designed questionnaire was delivered to community residents in Changsha (the capital city of Hunan province) with a total of 1,249 completed forms returned and statistically analyzed. The majority of the participants considered that brain donation would help medical research and education, and 32.0% of respondents agreed that the brain donation would help change the traditional Chinese funeral belief in keeping the body intact after death. However, participants aged over 60 years old were less supportive of this concept. Among all participants, 63.7% stated that they were not knowledgeable about brain donation, while 26.4% explicitly expressed a willingness to participate in brain donation. Age, gender, monthly household income, and knowledge about brain donation significantly affected the willingness. Compared with other age groups, a higher proportion of participants aged over 60 years old preferred to be informed by a medical college. To promote brain donation in China, especially among the elderly, better communication of its medical benefits and a reinterpretation of the Confucius view of the human body should be provided. Efforts are also needed to provide appropriate forums and sources of brain donation information to targeted communities and society in general.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ase.1886DOI Listing
January 2020

Reappraisal of the Mawangdui Han Tomb Cadaver Thirty Years After Its Unearthing.

Biopreserv Biobank 2019 Apr 28;17(2):98-104. Epub 2019 Mar 28.

1 Department of Anatomy and Neurobiology, Central South University Xiangya School of Medicine, Changsha, Hunan, China.

The Mawangdui tomb No.1 cadaver, a female corpse from the Western Han Dynasty, was unearthed in 1972. Forensic examination at the time of discovery indicated fairly remarkable presence of bodily constituents at the anatomical, histological, and molecular levels. The cadaver was preserved in a formalin-based fixative afterward, and maintained in the Hunan Museum. To better protect this rare human corpse, a reappraisal of the status of preservation was carried out using noninvasive approaches, including X-ray radiography, gross anatomical examination, and histological, microbiological, and molecular analyses of sampled tissues. The cadaver remained essentially intact from a gross anatomical perspective, with radiography of the skeletal system and arterial contrast filling appeared comparable with the original documentation. The light microscopic features of the skin, cartilage, and skeletal muscle remained detectable, as were the stratified ultrastructure of the collagen and muscle fibers. The levels of nitrogen and amino acidic elements appeared elevated in the cadaver and liver preservation fixatives, with a higher calcium and phosphate concentration in the former. These findings suggest that there existed a certain degree of macromolecule degradation and bone decalcification in the cadaver, likely irrelevant to biological decomposition. The reappraisal also led to the implementation of stronger scientific measures to better protect the cadaver through a renovated Museum-University coadministrative management agreement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/bio.2019.0002DOI Listing
April 2019

Autopsy and Forensic Study on a Rare Human Corpse Preserved Over Two Thousand Years: The Mawangdui Ancient Cadaver.

Biopreserv Biobank 2019 Apr 28;17(2):105-112. Epub 2019 Mar 28.

1 Department of Anatomy and Neurobiology, Central South University Xiangya School of Medicine, Changsha, Hunan, China.

In 1972, an enormous tomb site was found in the eastern suburb of Changsha, the capital city of Hunan Province, which led to the discovery of Mawangdui tomb No. 1, and soon thereafter tombs Nos. 2 and 3. These tombs were dated back to the Western Han Dynasty (206 BC-24 AD) in Chinese history. Along with numerous precious historic relics unearthed as grave goods, a well-preserved female cadaver was the most unprecedented, which was considered as one of the world's greatest archeological discoveries in the 20th century. The cadaver was initially examined through autopsy and X-ray imaging, with biopsies from multiple body parts analyzed histologically at the light and electron microscopic levels. In this review, we summarize the major imaging and autopsy findings from the cadaver indicative of remarkable preservation of some histological, cellular, and molecular constituents of the body. A forensic assessment of antemortem illnesses and potential cause of death of the subject are also noted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/bio.2019.0001DOI Listing
April 2019

Special Section: A Well-Preserved 2000-Year-Old Chinese Cadaver.

Biopreserv Biobank 2019 Apr 28;17(2):93-94. Epub 2019 Mar 28.

1 Department of Anatomy and Neurobiology, Central South University, Xiangya School of Medicine, Changsha, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/bio.2019.29049.xxyDOI Listing
April 2019

Regional and Cellular Mapping of Sortilin Immunoreactivity in Adult Human Brain.

Front Neuroanat 2019 12;13:31. Epub 2019 Mar 12.

Department of Anatomy and Neurobiology, Xiangya School of Medicine, Central South University, Changsha, China.

Sortilin is a member of the vacuolar protein sorting 10 protein (VPS10P) domain receptor family, which carries out signal transduction and protein transport in cells. Sortilin serves as the third, G-protein uncoupled, receptor of neurotensin that can modulate various brain functions. More recent data indicate an involvement of sortilin in mood disorders, dementia and Alzheimer-type neuropathology. However, data regarding the normal pattern of regional and cellular expression of sortilin in the human brain are not available to date. Using postmortem adult human brains free of neuropathology, the current study determined sortilin immunoreactivity (IR) across the entire brain. Sortilin IR was broadly present in the cerebrum and subcortical structures, localizing to neurons in the somatodendritic compartment, but not to glial cells. In the cerebrum, sortilin IR exhibited differential regional and laminar patterns, with pyramidal, multipolar and polymorphic neurons in cortical layers II-VI, hippocampal formation and amygdaloid complex more distinctly labeled relative to GABAergic interneurons. In the striatum and thalamus, numerous small-to-medium sized neurons showed light IR, with a small group of large sized neurons heavily labeled. In the midbrain and brainstem, sortilin IR was distinct in neurons at the relay centers of descending and ascending neuroanatomical pathways. Dopaminergic neurons in the substantia nigra, cholinergic neurons in the basal nuclei of Meynert and noradrenergic neurons in the locus coeruleus co-expressed strong sortilin IR in double immunofluorescence. In comparison, sortilin IR was weak in the olfactory bulb and cerebellar cortex, with the mitral and Purkinje cells barely visualized. A quantitative analysis was carried out in the lateral, basolateral, and basomedial nuclei of the amygdaloid complex, as well as cortical layers II-VI, which established a positive correlation between the somal size and the intensity of sortilin IR among labeled neurons. Together, the present study demonstrates a predominantly neuronal expression of sortilin in the human brain with substantial regional and cell-type variability. The enriched expression of sortilin in pyramidal, dopaminergic, noradrenergic and cholinergic neurons suggests that this protein may be particularly required for signal transduction, protein trafficking and metabolic homeostasis in populations of relatively large-sized projective neurons.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnana.2019.00031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6422922PMC
March 2019

Mawangdui-Type Ancient Human Cadavers in China and Strategies for Their Long-Term Preservation.

Biopreserv Biobank 2019 Apr 19;17(2):113-118. Epub 2019 Mar 19.

1 Department of Anatomy and Neurobiology, Central South University Xiangya School of Medicine, Changsha, Hunan, China.

Ancient human remains may exist as intact cadavers in various forms, including mummies as well as humid or soft corpses. These valuable human depositories have been increasingly investigated with modern molecular biological approaches, delivering breakthrough discoveries in the field of paleoanthropology. Many ancient remains are also preserved in museums for public education of the history of human civilization. The Mawangdui tomb No. 1 cadaver was unearthed in 1972 in Changsha, China, and is a well-preserved humid-type corpse of a deceased woman who lived in the Western Han Dynasty (206BC-24AD). During the past few decades, a number of other similar cadavers have been discovered in China. The Mawangdui cadaver thus appears to represent an archetype of the humid corpses that are commonly unearthed from buried coffins, but show a great extent of anatomical and histological integrity at the time of excavation. Long-term protection of these cadavers is important with regard to scientific investigation and heritage conservation, while challenges exist to develop effective preservation protocols. In this perspective article, we describe the overall features of the humid cadavers found in China, and discuss the factors that potentially contributed to their preservation before excavation. We also introduce the efforts taken for, and experience learned from, postexcavation preservation of the Mawangdui cadaver during the past four decades. Finally, we propose that research into the mechanism governing the breakdown of macromolecules may provide potential solutions for extended protection of these valuable ancient human remains.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/bio.2019.0018DOI Listing
April 2019

Progress in Human Brain Banking in China.

Neurosci Bull 2019 Apr 7;35(2):179-182. Epub 2019 Mar 7.

Department Neuropsychiatric Disorders, Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12264-019-00350-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6426891PMC
April 2019

Impaired Glucose Tolerance and Reduced Plasma Insulin Precede Decreased AKT Phosphorylation and GLUT3 Translocation in the Hippocampus of Old 3xTg-AD Mice.

J Alzheimers Dis 2019 ;68(2):809-837

Department of Physiology, Southern Illinois University School of Medicine, Carbondale, IL, USA.

Several studies have demonstrated that mouse models of Alzheimer's disease (AD) can exhibit impaired peripheral glucose tolerance. Further, in the APP/PS1 mouse model, this is observed prior to the appearance of AD-related neuropathology (e.g., amyloid-β plaques; Aβ) or cognitive impairment. In the current study, we examined whether impaired glucose tolerance also preceded AD-like changes in the triple transgenic model of AD (3xTg-AD). Glucose tolerance testing (GTT), insulin ELISAs, and insulin tolerance testing (ITT) were performed at ages prior to (1-3 months and 6-8 months old) and post-pathology (16-18 months old). Additionally, we examined for altered insulin signaling in the hippocampus. Western blots were used to evaluate the two-primary insulin signaling pathways: PI3K/AKT and MAPK/ERK. Since the PI3K/AKT pathway affects several downstream targets associated with metabolism (e.g., GSK3, glucose transporters), western blots were used to examine possible alterations in the expression, translocation, or activation of these targets. We found that 3xTg-AD mice display impaired glucose tolerance as early as 1 month of age, concomitant with a decrease in plasma insulin levels well prior to the detection of plaques (∼14 months old), aggregates of hyperphosphorylated tau (∼18 months old), and cognitive decline (≥18 months old). These alterations in peripheral metabolism were seen at all time points examined. In comparison, PI3K/AKT, but not MAPK/ERK, signaling was altered in the hippocampus only in 18-20-month-old 3xTg-AD mice, a time point at which there was a reduction in GLUT3 translocation to the plasma membrane. Taken together, our results provide further evidence that disruptions in energy metabolism may represent a foundational step in the development of AD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/JAD-180707DOI Listing
July 2020

Subarachnoid hemorrhage enhances the expression of TDP-43 in the brain of experimental rats and human subjects.

Exp Ther Med 2018 Oct 21;16(4):3363-3368. Epub 2018 Aug 21.

Department of Neurosurgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China.

The transactive response DNA-binding protein of 43 (TDP-43) may be involved in neurodegenerative disease and in the response to brain injury; however, alterations in the expression of TDP-43 following subarachnoid hemorrhage (SAH) require further investigation. The present study reported a notable elevation in the expression of TDP-43 within the cerebrospinal fluid (CSF) of patients with aneurysmal SAH and increased brain expression of TDP-43 in a rat model of SAH. The TDP-43 protein and a derivative migrated at 43 and 24 kDa, respectively, as observed via the immunoblotting of concentrated CSF samples obtained from patients with SAH; no signal was detected in the CSF from healthy controls. SAH in rats was induced by intravascular suture puncture. The expression levels of TDP-43 in rat cortical lysates following SAH were increased at 0.5 h, peaked at 48 h and remained significantly elevated at 72 h post-injury, compared with sham controls. TDP-43 immunolabeling indication localization within neurons, astrocytes and microglia in the experimental rats. Collectively, the findings of the present study indicated the early involvement of TDP-43 in the brain in response to SAH, and that expression levels of TDP-43 in the CSF may serve as a prognostic biomarker among patients with this condition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/etm.2018.6636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6143865PMC
October 2018

Lack of human-like extracellular sortilin neuropathology in transgenic Alzheimer's disease model mice and macaques.

Alzheimers Res Ther 2018 04 24;10(1):40. Epub 2018 Apr 24.

Department of Anatomy and Neurobiology, Central South University School of Basic Medical Science, Changsha, 410013, Hunan, China.

Background: Alzheimer's disease (AD) is a devastating neurodegenerative disorder bearing multiple pathological hallmarks suggestive of complex cellular/molecular interplay during pathogenesis. Transgenic mice and nonhuman primates are used as disease models for mechanistic and translational research into AD; the extent to which these animal models recapitulate AD-type neuropathology is an issue of importance. Putative C-terminal fragments from sortilin, a member of the vacuolar protein sorting 10 protein (Vps10p) family, have recently been shown to deposit in the neuritic β-amyloid (Aβ) plaques in the human brain.

Methods: We set out to explore if extracellular sortilin neuropathology exists in AD-related transgenic mice and nonhuman primates. Brains from different transgenic strains and ages developed overt cerebral Aβ deposition, including the β-amyloid precursor protein and presenilin 1 double-transgenic (APP/PS1) mice at ~ 14 months of age, the five familial Alzheimer's disease mutations transgenic (5×FAD) mice at ~ 8 months, the triple-transgenic Alzheimer's disease (3×Tg-AD) mice at ~ 22 months, and aged monkeys (Macaca mulatta and Macaca fascicularis) were examined. Brain samples from young transgenic mice, middle-aged/aged monkeys, and AD humans were used as negative and positive pathological controls.

Results: The C-terminal sortilin antibody, which labeled senile plaques in the AD human cerebral sections, did not display extracellular immunolabeling in the transgenic mouse or aged monkey brain sections with Aβ deposition. In Western blot analysis, sortilin fragments ~ 15 kDa were not detectable in transgenic mouse cortical lysates, but they occurred in control AD lysates.

Conclusions: In reference to their human brain counterparts, neuritic plaques seen in transgenic AD model mouse brains represent an incomplete form of this AD pathological hallmark. The species difference in neuritic plaque constituents also indicates more complex secondary proteopathies in the human brain relative to rodents and nonhuman primates during aging and in AD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13195-018-0370-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5978992PMC
April 2018

Sortilin: a new player in dementia and Alzheimer-type neuropathology.

Biochem Cell Biol 2018 10 24;96(5):491-497. Epub 2018 Apr 24.

a Department of Anatomy and Neurobiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, China.

Age-related dementias are now a major mortality factor among most human populations in the world, with Alzheimer's disease (AD) being the leading dementia-causing neurodegenerative disease. The pathogenic mechanism underlying dementia disorders, and AD in particular, remained largely unknown. Efforts to develop drugs targeting the disease's hallmark lesions, such as amyloid plaque and tangle pathologies, have been unsuccessful so far. The vacuolar protein sorting 10p (Vps10p) family plays a critical role in membrane signal transduction and protein sorting and trafficking between intracellular compartments. Data emerging during the past few years point to an involvement of this family in the development of AD. Specifically, the Vps10p member sortilin has been shown to participate in amyloid plaque formation, tau phosphorylation, abnormal protein sorting and apoptosis. In this minireview, we update some latest findings from animal experiments and human brain studies suggesting that abnormal sortilin expression is associated with AD-type neuropathology, warranting further research that might lead to novel targets for the development of AD therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1139/bcb-2018-0023DOI Listing
October 2018

Can brain impermeable BACE1 inhibitors serve as anti-CAA medicine?

BMC Neurol 2017 Aug 25;17(1):163. Epub 2017 Aug 25.

Department of Neurology & Key Laboratory of Hunan Province in Neurodegenerative Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.

Background: Cerebral amyloid angiopathy (CAA) is characterized by the deposition of ß-amyloid peptides (Aß) in and surrounding the wall of microvasculature in the central nervous system, together with parenchymal amyloid plaques collectively referred to as cerebral amyloidosis, which occurs in the brain commonly among the elderly and more frequently in patients with Alzheimer's disease (AD). CAA is associated with vascular injury and may cause devastating neurological outcomes. No therapeutic approach is available for this lesion to date.

Main Body: ß-Secretase 1 (BACE1) is the enzyme initiating Aß production. Brain permeable BACE1 inhibitors targeting primarily at the parenchymal plaque pathology are currently evaluated in clinical trials. This article presents findings in support of a role of BACE1 elevation in the development of CAA, in addition to plaque pathogenesis. The rationale, feasibility, benefit and strategic issues for developing BACE1 inhibitors against CAA are discussed. Brain impermeable compounds are considered preferable as they might exhibit sufficient anti-CAA efficacy without causing significant neuronal/synaptic side effects.

Conclusion: Early pharmacological intervention to the pathogenesis of CAA is expected to provide significant protection for cerebral vascular health and hence brain health. Brain impermeable BACE1 inhibitors should be optimized and tested as potential anti-CAA therapeutics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12883-017-0942-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5574137PMC
August 2017

Early-life lipopolysaccharide exposure potentiates forebrain expression of NLRP3 inflammasome proteins and anxiety-like behavior in adolescent rats.

Brain Res 2017 Sep 24;1671:43-54. Epub 2017 Jun 24.

Department of Anatomy and Neurobiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, China. Electronic address:

Background: Neonatal inflammation may affect brain development and lead to cognitive and emotional deficits at adolescence and adulthood. The nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) is the core component of NLRP3 inflammasome, which may involve in neuroinflammation. We explored if early-life exposure to the bacterial endotoxin lipopolysaccharide (LPS) could promote the expression of proteins related to NLRP3 inflammasome, including NLRP3, the apoptosis-associated speck-like protein (ASC) and cysteiny aspartate-specific protease (Caspase-1) in the forebrain, and behavioral alteration in adolescent rats.

Methods: Two-week old Sprague Dawley rats were divided into naïve control, vehicle (phosphate buffered saline, PBS) control and LPS (100μg/kg, i.p.) treatment groups. Anxiety and depression-like behaviors were examined around 1month age, with the expression of NLRP3, ASC and Caspase-1 in the prefrontal cortex (PFC) and hippocampus analyzed by means of immunohistochemistry and western blot.

Results: LPS-treated rats exhibited anxiety but not depressive-like behavior as indicated by results of open field, elevated plus maze, dark-light box, sucrose preference and forced swimming tests. Increased immunolabeling of NLRP3, ASC and Caspase-1 in neurons and/or microglia occurred in the PFC and hippocampus in LPS-treated adolescents relative to controls, with immunoblot shown elevated levels of these proteins.

Conclusion: Early-life inflammatory stress promotes the expression of NLRP3 inflammasome proteins in the brain and the occurrence of anxiety-like behavior in adolescent rats.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.brainres.2017.06.014DOI Listing
September 2017

Sortilin Fragments Deposit at Senile Plaques in Human Cerebrum.

Front Neuroanat 2017 7;11:45. Epub 2017 Jun 7.

Department of Anatomy and Neurobiology, Central South University School of Basic Medical ScienceChangsha, China.

Genetic variations in the vacuolar protein sorting 10 protein (Vps10p) family have been linked to Alzheimer's disease (AD). Here we demonstrate deposition of fragments from the Vps10p member sortilin at senile plaques (SPs) in aged and AD human cerebrum. Sortilin changes were characterized in postmortem brains with antibodies against the extracellular and intracellular C-terminal domains. The two antibodies exhibited identical labeling in normal human cerebrum, occurring in the somata and dendrites of cortical and hippocampal neurons. The C-terminal antibody also marked extracellular lesions in some aged and all AD cases, appearing as isolated fibrils, mini-plaques, dense-packing or circular mature-looking plaques. Sortilin and β-amyloid (Aβ) deposition were correlated overtly in a region/lamina- and case-dependent manner as analyzed in the temporal lobe structures, with co-localized immunofluorescence seen at individual SPs. However, sortilin deposition rarely occurred around the pia, at vascular wall or in areas with typical diffuse Aβ deposition, with the labeling not enhanced by section pretreatment with heating or formic acid. Levels of a major sortilin fragment ~15 kDa, predicted to derive from the C-terminal region, were dramatically elevated in AD relative to control cortical lysates. Thus, sortilin fragments are a prominent constituent of the extracellularly deposited protein products at SPs in human cerebrum.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnana.2017.00045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5461299PMC
June 2017

Blood DNA methylation pattern is altered in mesial temporal lobe epilepsy.

Sci Rep 2017 03 9;7:43810. Epub 2017 Mar 9.

Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

Mesial temporal lobe epilepsy (MTLE) is a common epileptic disorder; little is known whether it is associated with peripheral epigenetic changes. Here we compared blood whole genomic DNA methylation pattern in MTLE patients (n = 30) relative to controls (n = 30) with the Human Methylation 450 K BeadChip assay, and explored genes and pathways that were differentially methylated using bioinformatics profiling. The MTLE and control groups showed significantly different (P < 1.03e-07) DNA methylation at 216 sites, with 164 sites involved hyper- and 52 sites hypo- methylation. Two hyper- and 32 hypo-methylated sites were associated with promoters, while 87 hyper- and 43 hypo-methylated sites corresponded to coding regions. The differentially methylated genes were largely related to pathways predicted to participate in anion binding, oxidoreductant activity, growth regulation, skeletal development and drug metabolism, with the most distinct ones included SLC34A2, CLCN6, CLCA4, CYP3A43, CYP3A4 and CYP2C9. Among the MTLE patients, panels of genes also appeared to be differentially methylated relative to disease duration, resistance to anti-epileptics and MRI alterations of hippocampal sclerosis. The peripheral epigenetic changes observed in MTLE could be involved in certain disease-related modulations and warrant further translational investigations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/srep43810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343463PMC
March 2017

Glucose tolerance and insulin sensitivity are impaired in APP/PS1 transgenic mice prior to amyloid plaque pathogenesis and cognitive decline.

Exp Gerontol 2017 02 23;88:9-18. Epub 2016 Dec 23.

Department of Physiology, Southern Illinois University School of Medicine, Carbondale, IL 62901, USA; Department of Anatomy, Southern Illinois University School of Medicine, Carbondale, IL 62901, USA; Center for Integrated Research in Cognitive and Neural Sciences, Southern Illinois University, Carbondale, IL 62901, USA. Electronic address:

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by beta-amyloid (Aβ) deposition, neurofibrillary tangles and cognitive decline. Clinical data suggests that both type 1 and type 2 diabetes are risk factors for AD-related dementia and several clinical studies have demonstrated that AD patients show alterations in peripheral glucose regulation characterized by insulin resistance (hyperinsulinemia) or hypoinsulinemia. Whether animal models of AD exhibit a pre-diabetic phenotype without additional dietary or experimental manipulation is unclear however, with contradictory data available. Further, most studies have not examined the time course of potential pre-diabetic changes relative to AD pathogenesis and cognitive decline. Thus, in this study we tested the hypothesis that a pre-diabetic phenotype (peripheral metabolic dysregulation) exists in the APP/PS1 transgenic model of AD under normal conditions and precedes AD-related pathology. Specifically, we examined glucose tolerance in male APP/PS1 mice on a C57BL/6J congenic background at 2, 4-6 and 8-9months of age by assessing fasting glucose levels, glucose tolerance, plasma insulin levels and insulin sensitivity as well as the development of pathological characteristics of AD and verified that our APP/PS1 mice develop cognitive impairment. Here we show that APP/PS1 mice, compared to wild-type controls, exhibit a significant impairment in glucose tolerance during an intraperitoneal glucose tolerance test (ipGTT) and a trend for increased fasting plasma insulin concentrations as early as 2months of age, while extracellular Aβ deposition occurs later and cognitive decline exists at 8-9months of age. Moreover, APP/PS1 mice did not respond as well to exogenous insulin as the wild-type controls during an intraperitoneal insulin tolerance test (ipITT). Taken together, these data reveal that male APP/PS1 mice on a C57BL/6J congenic background exhibit a pre-diabetic phenotype prior to the development of AD-like pathology and that this metabolic deficit persists when they exhibit neuropathology and cognitive decline. This raises the question of whether altered glucose regulation and insulin production/secretion could contribute to AD pathogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.exger.2016.12.019DOI Listing
February 2017

Aberrant expression of the pore-forming K channel subunit Kir6.2 in hippocampal reactive astrocytes in the 3xTg-AD mouse model and human Alzheimer's disease.

Neuroscience 2016 Nov 29;336:81-101. Epub 2016 Aug 29.

Department of Physiology, Southern Illinois University School of Medicine, Carbondale, IL 62901, USA; Department of Anatomy, Southern Illinois University School of Medicine, Carbondale, IL 62901, USA; Center for Integrated Research in Cognitive and Neural Sciences, Southern Illinois University Carbondale, IL 62901, USA. Electronic address:

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by beta-amyloid (Aβ) deposition, neurofibrillary tangles and cognitive decline. Recent pharmacologic studies have found that ATP-sensitive potassium (K) channels may play a role in AD and could be a potential therapeutic target. Interestingly, these channels are found in both neurons and astrocytes. One of the hallmarks associated with AD is reactive gliosis and a change in astrocytic function has been identified in several neuropathological conditions including AD. Thus the goal of this study was to examine whether the pore-forming subunits of K channels, Kir6.1 and Kir6.2, are altered in the hippocampus in a cell type-specific manner of the 3xTg-AD mouse model of AD and in human AD tissue obtained from the Chinese brain bank. Specifically, in old 3xTg-AD mice, and age-matched controls, we examined glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), Kir6.1 and Kir6.2 in hippocampal region CA1 with a combination of immunoblotting and immunohistochemistry (IHC). A time point was selected when memory impairment and histopathological changes have been reported to occur in 3xTg-AD mice. In human AD and age-matched control tissue IHC experiments were performed using GFAP and Kir6.2. In the hippocampus of 3xTg-AD mice, compared to wild-type controls, Western blots showed a significant increase in GFAP indicating astrogliosis. Further, there was an increase in Kir6.2, but not Kir6.1 in the plasma membrane fraction. IHC examination of hippocampal region CA1 in 3xTg-AD sections revealed an increase in Kir6.2 immunoreactivity (IR) in astrocytes as identified by GFAP and GS. In human AD tissue similar data were obtained. There was an increase in GFAP-IR in the stratum oriens (SO) and alveus (ALV) of CA1 concomitant with an increase in Kir6.2-IR in cells with an astrocytic-like morphology. Dual immunofluorescence revealed a dramatic increase in co-localization of Kir6.2-IR and GFAP-IR. Taken together, these data demonstrate that increased Kir6.2 is seen in reactive astrocytes in old 3xTg-AD mice and human AD tissue. These changes could dramatically alter astrocytic function and subsequently contribute to AD phenotype in either a compensatory or pathophysiological manner.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroscience.2016.08.034DOI Listing
November 2016

Quantitative protein profiling of hippocampus during human aging.

Neurobiol Aging 2016 Mar 8;39:46-56. Epub 2015 Dec 8.

Department of Human Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China. Electronic address:

The hippocampus appears commonly affected by aging and various neurologic disorders in humans, whereas little is known about age-related change in overall protein expression in this brain structure. Using the 4-plex tandem mass tag labeling, we carried out a quantitative proteomic study of the hippocampus during normal aging using postmortem brains from Chinese subjects. Hippocampal samples from 16 subjects died of non-neurological/psychiatric diseases were divided into 4 age groups: 22-49, 50-69, 70-89, and >90. Among 4582 proteins analyzed, 35 proteins were significantly elevated, whereas 25 proteins were downregulated, along with increasing age. Several upregulated proteins, including transgelin, vimentin, myosin regulatory light polypeptide 9, and calcyphosin, were further verified by quantitative Western blot analysis of hippocampal tissues from additional normal subjects. Bioinformatic analysis showed that the upregulated and downregulated proteins were largely involved in several important protein-protein interaction networks. Proteins in the electron transport chain and synaptic vesicle fusion pathway were consistently downregulated with aging, whereas proteins associated with Alzheimer's disease showed little change. Our study demonstrates substantial protein profile changes in the human hippocampus during aging, which could be of relevance to age-related loss of hippocampal functions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neurobiolaging.2015.11.029DOI Listing
March 2016

DNA-Binding, Photocleavage, and Photodynamic Anti-cancer Activities of Pyridyl Corroles.

J Membr Biol 2016 08 19;249(4):419-28. Epub 2016 Feb 19.

School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, 510641, People's Republic of China.

The DNA-binding, photocleavage, and antitumor activity of three free base pyridyl corroles 1, 2, and 3 have been investigated. The binding affinity toward CT-DNA decreases with increasing number of pentafluorophenyl, whereas the photocleavage activity toward pBR322 DNA becomes more efficient. Singlet oxygen was demonstrated as active species responsible for DNA cleavage. These corroles exhibited high cytotoxicity against three tested cancer cells (Hela, HapG2, and A549) and the cytotoxicity could be further enhanced under irradiation. Intracellular reactive oxygen species level was also monitored using HeLa Cells upon the combined treatment of corroles and light. These corroles could be absorbed by HeLa cells at low concentration. They can induce the decrease of mitochondrial membrane potential and apoptosis of tumor cells under irradiation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00232-016-9879-0DOI Listing
August 2016

SS31, a Small Molecule Antioxidant Peptide, Attenuates β-Amyloid Elevation, Mitochondrial/Synaptic Deterioration and Cognitive Deficit in SAMP8 Mice.

Curr Alzheimer Res 2016 ;13(3):297-306

Department of Neurology, Hebei General Hospital, Shijiazhuang, 050051, China.

Mitochondrial dysfunction, oxidative stress and β -amyloid (Aβ) formation are thought to cause neuronal and synaptic degeneration underlying cognitive decline in Alzheimer's disease (AD). The senescence-accelerated mouse-prone 8 (SAMP8) mice have been used as an animal model for mechanistic and translational research for AD. In the present study we characterized mitochondrial and synaptic alterations in SAMP8 mice relative to SAMR1control mice and explored a protective effect of the small molecule peptide SS31, a cell membrane penetrant antioxidant, on mitochondrial and synaptic protein integrity as well as cognitive performance. Electron microscopic analysis revealed mitochondrial/synaptic deterioration in 10 months-old SAMP8 relative to SAMR1 mice, with the changes in the former rescued following 8 weeks treatment with SS31 (5 mg/kg/day, i.p.). Elevation of Aβ42, mitochondrial fission protein (DLP1, Fis1) and matrix protein cyclophilin D (CypD), and reductions of mitochondrial fusion protein (Mfn2) and synaptic (i.e., synaptophysin, postsynaptic density protein 95 and growth associated protein 43) proteins, were detected in hippocampal lysates in SAMP8 mice relative to SAMR1. The above altered protein expressions in the SAMP8 mouse brain were restored with the SS31 treatment. Moreover, the SS31 treatment rescued learning and memory deficits detected in 10 month-old SAMP8 mice. Together, the findings suggest that this mitochondria-targeting antioxidant peptide may be of potential utility for AD therapy, with its pharmacological efficacy involves lowering of central Aβ levels and protection of mitochondrial homeostasis and synaptic integrity, which may help slow down cognitive decline.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1567205013666151218150004DOI Listing
December 2016

Neuroprotective Activities of Marine Natural Products from Marine Sponges.

Curr Med Chem 2016 ;23(4):360-82

Department of Medical Biotechnology, School of Medicine, Flinders University, Adelaide 5001, South Australia, Australia.

This review covers the compounds isolated from marine sponges with neuroprotective activities during the period between 1999 and 2014 based on their chemical structures, collections sites, sponge taxonomy and neuroprotective effects. These compounds were isolated from marine sponges collected from 18 countries, most of them in Indonesia, followed by Japan. A total of 90 compounds were reported to exhibit a range of neuroprotective efficacy. These compounds were shown to inhibit β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1), modulate the synthesis or activity of some neurotransmitters such as acetylcholinesterase and glutamate, enhancement of serotonin, reducing oxidative stress, inhibition of kinases and proteases, and enhancement of neurite growth. None of them have yet progressed into any marine pharmaceutical development pipeline, therefore sustained researches will be required to enhance the potential of utilizing these compounds in the future for prevention and therapeutic treatment of neurodegenerative diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/0929867323666151127201249DOI Listing
October 2016

Effects of total saponins of Panax notoginseng on immature neuroblasts in the adult olfactory bulb following global cerebral ischemia/reperfusion.

Neural Regen Res 2015 Sep;10(9):1450-6

Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, China.

The main active components extracted from Panax notoginseng are total saponins. They have been shown to inhibit platelet aggregation, increase cerebral blood flow, improve neurological behavior, decrease infarct volume and promote proliferation and differentiation of neural stem cells in the hippocampus and lateral ventricles. However, there is a lack of studies on whether total saponins of Panax notoginseng have potential benefits on immature neuroblasts in the olfactory bulb following ischemia and reperfusion. This study established a rat model of global cerebral ischemia and reperfusion using four-vessel occlusion. Rats were administered total saponins of Panax notoginseng at 75 mg/kg intraperitoneally 30 minutes after ischemia then once a day, for either 7 or 14 days. Total saponins of Panax notoginseng enhanced the number of doublecortin (DCX)(+) neural progenitor cells and increased co-localization of DCX with neuronal nuclei and phosphorylated cAMP response element-binding/DCX(+) neural progenitor cells in the olfactory bulb at 7 and 14 days post ischemia. These findings indicate that following global brain ischemia/reperfusion, total saponins of Panax notoginseng promote differentiation of DCX(+) cells expressing immature neuroblasts in the olfactory bulb and the underlying mechanism is related to the activation of the signaling pathway of cyclic adenosine monophosphate response element binding protein.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/1673-5374.165514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4625511PMC
September 2015