4,256 results match your criteria Neurobiology of disease[Journal]


Modeling neuronopathic storage diseases with patient-derived culture systems.

Neurobiol Dis 2019 Feb 18. Epub 2019 Feb 18.

Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. Electronic address:

Lysosomes are organelles involved in the degradation and recycling of macromolecules, and play a critical role in sensing metabolic information in the cell. A class of rare metabolic diseases called lysosomal storage disorders (LSD) are characterized by lysosomal dysfunction and the accumulation of macromolecular substrates. The central nervous system appears to be particularly vulnerable to lysosomal dysfunction, since many LSDs are characterized by severe, widespread neurodegeneration with pediatric onset. Read More

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http://dx.doi.org/10.1016/j.nbd.2019.01.018DOI Listing
February 2019

Fragile X mental retardation protein positively regulates PKA anchor Rugose and PKA activity to control actin assembly in learning/memory circuitry.

Neurobiol Dis 2019 Feb 13. Epub 2019 Feb 13.

Vanderbilt Brain Institute, Departments of Biological Sciences, Cell and Developmental Biology, and Pharmacology, Vanderbilt University and Medical Center, Nashville, TN 37235, USA. Electronic address:

Recent work shows Fragile X Mental Retardation Protein (FMRP) drives the translation of very large proteins (>2000 aa) mediating neurodevelopment. Loss of function results in Fragile X syndrome (FXS), the leading heritable cause of intellectual disability (ID) and autism spectrum disorder (ASD). Using the Drosophila FXS disease model, we discover FMRP positively regulates the translation of the very large A-Kinase Anchor Protein (AKAP) Rugose (>3000 aa), homolog of ASD-associated human Neurobeachin (NBEA). Read More

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http://dx.doi.org/10.1016/j.nbd.2019.02.004DOI Listing
February 2019
1 Read

Ubiquitylome profiling of Parkin-null brain reveals dysregulation of calcium homeostasis factors ATP1A2, Hippocalcin and GNA11, reflected by altered firing of noradrenergic neurons.

Neurobiol Dis 2019 Feb 11. Epub 2019 Feb 11.

Exp. Neurology, Goethe University Medical School, 60590 Frankfurt am Main, Germany. Electronic address:

Parkinson's disease (PD) is the second most frequent neurodegenerative disorder in the old population. Among its monogenic variants, a frequent cause is a mutation in the Parkin gene (Prkn). Deficient function of Parkin triggers ubiquitous mitochondrial dysfunction and inflammation in the brain, but it remains unclear how selective neural circuits become vulnerable and finally undergo atrophy. Read More

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http://dx.doi.org/10.1016/j.nbd.2019.02.008DOI Listing
February 2019
2 Reads

Synchronised spiking activity underlies phase amplitude coupling in the subthalamic nucleus of Parkinson's disease patients.

Neurobiol Dis 2019 Feb 9. Epub 2019 Feb 9.

MRC Brain Network Dynamics Unit, University of Oxford, Oxford OX1 3TH, United Kingdom. Electronic address:

Both phase-amplitude coupling (PAC) and beta-bursts in the subthalamic nucleus have been significantly linked to symptom severity in Parkinson's disease (PD) in humans and emerged independently as competing biomarkers for closed-loop deep brain stimulation (DBS). However, the underlying nature of subthalamic PAC is poorly understood and its relationship with transient beta burst-events has not been investigated. To address this, we studied macro- and micro electrode recordings of local field potentials (LFPs) and single unit activity from 15 hemispheres in 10 PD patients undergoing DBS surgery. Read More

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http://dx.doi.org/10.1016/j.nbd.2019.02.005DOI Listing
February 2019
1 Read

Inhibition and oscillations in the human brain tissue in vitro.

Neurobiol Dis 2019 Feb 8;125:198-210. Epub 2019 Feb 8.

Clinical Neurophysiology Department, Pitie-Salpetriere Hospital, Sorbonne Université, APHP, Paris 75013, France; Neuroglial Interactions in Cerebral Physiopathology, Center for Interdisciplinary Research in Biology, Collège de France, CNRS UMR 7241, INSERM U1050, Labex Memolife, PSL Research University, Paris 75005, France. Electronic address:

Oscillations represent basic operational modes of the human brain. They reflect local field potential activity generated by the laminar arrangement of cell-type specific microcircuits interacting brain-wide under the influence of neuromodulators, endogenous processes and cognitive demands. Under neuropathological conditions, the spatiotemporal structure of physiological brain oscillations is disrupted as recorded by electroencephalography and event-relate potentials. Read More

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http://dx.doi.org/10.1016/j.nbd.2019.02.006DOI Listing
February 2019
1 Read

GABA receptor-mediated networks during focal seizure onset and progression in vitro.

Neurobiol Dis 2019 Feb 8;125:190-197. Epub 2019 Feb 8.

Unit of Epileptology, Fondazione IRCCS Istituto Neurologico Carlo Besta, via Celoria 11, Milano, Italy.

Focal seizures are triggered by the pathological synchronization of a functionally altered group of neurons. In vivo and in vitro results in rodents and single unit studies in humans suggest that seizure can be initiated by increased activity in interneuronal networks. We review here the data derived from in vitro perparations to describe the function of GABAergic network in different phases of focal seizures. Read More

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http://dx.doi.org/10.1016/j.nbd.2019.02.007DOI Listing
February 2019
1 Read

Loss of biliverdin reductase-A favors Tau hyper-phosphorylation in Alzheimer's disease.

Neurobiol Dis 2019 Feb 6;125:176-189. Epub 2019 Feb 6.

Department of Biochemical Sciences "A. Rossi-Fanelli", Sapienza University of Rome, Piazzale A. Moro 5, Roma 00185, Italy. Electronic address:

Hyper-active GSK-3β favors Tau phosphorylation during the progression of Alzheimer's disease (AD). Akt is one of the main kinases inhibiting GSK-3β and its activation occurs in response to neurotoxic stimuli including, i.e. Read More

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http://dx.doi.org/10.1016/j.nbd.2019.02.003DOI Listing
February 2019
1 Read

Olfactory bulb atrophy and caspase activation observed in the BACHD rat models of Huntington disease.

Neurobiol Dis 2019 Feb 6;125:219-231. Epub 2019 Feb 6.

Research Center on Aging, Department of Pharmacology and Physiology, University of Sherbrooke, Sherbrooke, Canada. Electronic address:

Olfactory dysfunction is observed in several neurological disorders, including Huntington disease (HD), and correlates with global cognitive performance, depression and degeneration of olfactory regions in the brain. Despite clear evidence demonstrating olfactory dysfunction in HD patients, only limited details are available in murine models and the underlying mechanisms are unknown. In order to determine if alterations in the olfactory bulb (OB) are observed in HD we assessed OB weight or area from 3 to 12 months of age in the BACHD transgenic lines (TG5 and TG9). Read More

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https://linkinghub.elsevier.com/retrieve/pii/S09699961183023
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http://dx.doi.org/10.1016/j.nbd.2019.02.002DOI Listing
February 2019
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DLK regulates a distinctive transcriptional regeneration program after peripheral nerve injury.

Neurobiol Dis 2019 Feb 5. Epub 2019 Feb 5.

Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address:

Following damage to a peripheral nerve, injury signaling pathways converge in the cell body to generate transcriptional changes that support axon regeneration. Here, we demonstrate that dual leucine zipper kinase (DLK), a central regulator of injury responses including axon regeneration and neuronal apoptosis, is required for the induction of the pro-regenerative transcriptional program in response to peripheral nerve injury. Using a sensory neuron-conditional DLK knockout mouse model, we show a time course for the dependency of gene expression changes on the DLK pathway after sciatic nerve injury. Read More

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http://dx.doi.org/10.1016/j.nbd.2019.02.001DOI Listing
February 2019

Maternal immune activation impairs cognitive flexibility and alters transcription in frontal cortex.

Neurobiol Dis 2019 Feb 2;125:211-218. Epub 2019 Feb 2.

Department of Psychiatry, University of California San Diego, CA 9500 Gilman Drive, La Jolla, CA 92093, United States; VISN-22 Mental Illness Research, Education and Clinical Center (MIRECC), VA San Diego Healthcare System, La Jolla, CA, United States. Electronic address:

Background: Epidemiological studies suggest that the risk of neurodevelopmental disorders such as autism spectrum disorder (ASD) and schizophrenia is increased by prenatal exposure to viral or bacterial infection during pregnancy. It is still unclear how activation of the maternal immune response interacts with underlying genetic factors to influence observed ASD phenotypes.

Methods: The current study investigated how maternal immune activation (MIA) in mice impacts gene expression in the frontal cortex in adulthood, and how these molecular changes relate to deficits in cognitive flexibility and social behavior, and increases in repetitive behavior that are prevalent in ASD. Read More

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http://dx.doi.org/10.1016/j.nbd.2019.01.025DOI Listing
February 2019
4 Reads

Synergistic action of CB and 5-HT receptors in preventing pilocarpine-induced status epilepticus in rats.

Neurobiol Dis 2019 Feb 1;125:135-145. Epub 2019 Feb 1.

Laboratory of Neurophysiology, Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, Msida, Malta; School of Biosciences, Cardiff University, Cardiff, UK. Electronic address:

Endocannabinoids (eCBs) and serotonin (5-HT) play a neuromodulatory role in the central nervous system. Both eCBs and 5-HT regulate neuronal excitability and their pharmacological potentiation has been shown to control seizures in pre-clinical and human studies. Compelling evidence indicates that eCB and 5-HT systems interact to modulate several physiological and pathological brain functions, such as food intake, pain, drug addiction, depression, and anxiety. Read More

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http://dx.doi.org/10.1016/j.nbd.2019.01.026DOI Listing
February 2019
2 Reads

Insights into GBA Parkinson's disease pathology and therapy with induced pluripotent stem cell model systems.

Neurobiol Dis 2019 Jan 31. Epub 2019 Jan 31.

German Center for Neurodegenerative Diseases (DZNE), 72076 Tübingen, Germany; Center of Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Germany. Electronic address:

While the link between GBA and Parkinson's disease (PD) was initially unexpected, it is now well established that GBA mutations are the most frequent genetic risk for PD. GBA has also been linked to sporadic PD, dementia with Lewy bodies, and ageing. Thus, GBA represents a promising target to counteract brain disease and the age-related decline of lysosomal function. Read More

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http://dx.doi.org/10.1016/j.nbd.2019.01.023DOI Listing
January 2019
2 Reads

Mannitol decreases neocortical epileptiform activity during early brain development via cotransport of chloride and water.

Neurobiol Dis 2019 Feb 1;125:163-175. Epub 2019 Feb 1.

Department of Neurology, Massachusetts General Hospital, Boston 02114, United States; Harvard Medical School, Boston, MA 02115, United States.

Seizures and brain injury lead to water and Cl accumulation in neurons. The increase in intraneuronal Cl concentration ([Cl]) depolarizes the GABA reversal potential (E) and worsens seizure activity. Neocortical neuronal membranes have a low water permeability due to the lack of aquaporins necessary to move free water. Read More

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http://dx.doi.org/10.1016/j.nbd.2019.01.024DOI Listing
February 2019
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Role of pedunculopontine nucleus in sleep-wake cycle and cognition in humans: A systematic review of DBS studies.

Neurobiol Dis 2019 Jan 30. Epub 2019 Jan 30.

Neurosciences Research Centre, Molecular and Clinical Sciences Research Institute, St George's University of London, London, United Kingdom; Department of Experimental and Clinical Medicine, University of Messina, Italy. Electronic address:

Background: Animal studies have demonstrated that the pedunculopontine nucleus (PPN) is involved in the control of posture and gait, and that it is also a key structure in controlling basic non-motor functions such as sleep, attention and arousal. In this systematic review we aimed to evaluate all available studies assessing the role of PPN on cognition, nocturnal sleep and alertness in humans. Finally, we attempted to define a model in which PPN acts as an interface structure between motor control and behavior. Read More

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http://dx.doi.org/10.1016/j.nbd.2019.01.022DOI Listing
January 2019

Multi-faceted therapeutic strategy for treatment of Alzheimer's disease by concurrent administration of etodolac and α-tocopherol.

Neurobiol Dis 2019 Jan 30;125:123-134. Epub 2019 Jan 30.

Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, 720 S. Donahue Dr., Auburn, AL 36849, USA. Electronic address:

Alzheimer's disease (AD) is a complex neurodegenerative disorder with multiple dysfunctional pathways. Therefore, a sophisticated treatment strategy that simultaneously targets multiple brain cell types and disease pathways could be advantageous for effective intervention. To elucidate an effective treatment, we developed an in vitro high-throughput screening (HTS) assay to evaluate candidate drugs for their ability to enhance the integrity of the blood-brain barrier (BBB) and improve clearance of amyloid-β (Aβ) using a cell-based BBB model. Read More

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http://dx.doi.org/10.1016/j.nbd.2019.01.020DOI Listing
January 2019
4 Reads
5.078 Impact Factor

MiR-146a promotes oligodendrocyte progenitor cell differentiation and enhances remyelination in a model of experimental autoimmune encephalomyelitis.

Neurobiol Dis 2019 Jan 29;125:154-162. Epub 2019 Jan 29.

Department of Neurology, Henry Ford Health System, Detroit, MI 48202, United States; Department of Physics, Oakland University, Rochester, MI 48309, United States.

The death of mature oligodendrocytes (OLs) leads to demyelination in the central nervous system (CNS) and subsequently to functional deficits. Remyelination requires the differentiation of oligodendrocyte progenitor cells (OPCs) into myelinating OLs, which in the CNS with neurodegenerative diseases such as multiple sclerosis (MS), is often inhibited. Among the inhibitors of OPC differentiation are toll-like receptor 2 (TLR2) and interleukin-1 receptor-associated kinase 1 (IRAK1) signaling, and both are negatively regulated by microRNA-146a (miR-146a). Read More

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http://dx.doi.org/10.1016/j.nbd.2019.01.019DOI Listing
January 2019
2 Reads
5.078 Impact Factor

Trihexyphenidyl rescues the deficit in dopamine neurotransmission in a mouse model of DYT1 dystonia.

Neurobiol Dis 2019 Jan 30;125:115-122. Epub 2019 Jan 30.

Department of Pharmacology, Emory University School of Medicine, 101 Woodruff Circle, WMB 6304, Atlanta, GA 30322, USA; Department of Neurology, Emory University School of Medicine, 101 Woodruff Circle, WMB 6304, Atlanta, GA 30322, USA. Electronic address:

Trihexyphenidyl, a nonselective muscarinic receptor antagonist, is the small molecule drug of choice for the treatment of DYT1 dystonia, but it is poorly tolerated due to significant side effects. A better understanding of the mechanism of action of trihexyphenidyl is needed for the development of improved treatments. Because DTY1 dystonia is associated with both abnormal cholinergic neurotransmission and abnormal dopamine regulation, we tested the hypothesis that trihexyphenidyl normalizes striatal dopamine release in a mouse model of DYT1 dystonia using ex vivo fast scan cyclic voltammetry and in vivo microdialysis. Read More

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http://dx.doi.org/10.1016/j.nbd.2019.01.012DOI Listing
January 2019
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Neuronal overexpression of Alzheimer's disease and Down's syndrome associated DYRK1A/minibrain gene alters motor decline, neurodegeneration and synaptic plasticity in Drosophila.

Neurobiol Dis 2019 Jan 28;125:107-114. Epub 2019 Jan 28.

School of Physiology, Pharmacology and Neuroscience, University of Bristol, University Walk, Bristol BS8 1TD, UK. Electronic address:

Down syndrome (DS) is characterised by abnormal cognitive and motor development, and later in life by progressive Alzheimer's disease (AD)-like dementia, neuropathology, declining motor function and shorter life expectancy. It is caused by trisomy of chromosome 21 (Hsa21), but how individual Hsa21 genes contribute to various aspects of the disorder is incompletely understood. Previous work has demonstrated a role for triplication of the Hsa21 gene DYRK1A in cognitive and motor deficits, as well as in altered neurogenesis and neurofibrillary degeneration in the DS brain, but its contribution to other DS phenotypes is unclear. Read More

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http://dx.doi.org/10.1016/j.nbd.2019.01.017DOI Listing
January 2019
1 Read

Child maltreatment and psychosis.

Neurobiol Dis 2019 Jan 24. Epub 2019 Jan 24.

Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, United States.

This paper reviews the literature on the association between experiences of child abuse and neglect and the development of psychoses. It then explores the premise that psychotic patients with a history of maltreatment may comprise a clinically and biological distinct subgroup. The review demonstrates that there is a growing consensus in the field that experiences of child maltreatment contribute to the onset of psychotic symptoms and psychotic disorders. Read More

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http://dx.doi.org/10.1016/j.nbd.2019.01.015DOI Listing
January 2019
5 Reads

Cannabinoid type-1 receptor blockade restores neurological phenotypes in two models for Down syndrome.

Neurobiol Dis 2019 Jan 25;125:92-106. Epub 2019 Jan 25.

Laboratory of Neuropharmacology-NeuroPhar, Department of Experimental and Health Sciences, University Pompeu Fabra, 08003 Barcelona, Spain. Electronic address:

Intellectual disability is the most limiting hallmark of Down syndrome, for which there is no gold-standard clinical treatment yet. The endocannabinoid system is a widespread neuromodulatory system involved in multiple functions including learning and memory processes. Alterations of this system contribute to the pathogenesis of several neurological and neurodevelopmental disorders. Read More

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http://dx.doi.org/10.1016/j.nbd.2019.01.014DOI Listing
January 2019
3 Reads

TDP-43 proteinopathy in aging: Associations with risk-associated gene variants and with brain parenchymal thyroid hormone levels.

Neurobiol Dis 2019 Jan 23;125:67-76. Epub 2019 Jan 23.

Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA; Department of Biostatistics, University of Kentucky, Lexington, KY, USA.

TDP-43 proteinopathy is very prevalent among the elderly (affecting at least 25% of individuals over 85 years of age) and is associated with substantial cognitive impairment. Risk factors implicated in age-related TDP-43 proteinopathy include commonly inherited gene variants, comorbid Alzheimer's disease pathology, and thyroid hormone dysfunction. To test parameters that are associated with aging-related TDP-43 pathology, we performed exploratory analyses of pathologic, genetic, and biochemical data derived from research volunteers in the University of Kentucky Alzheimer's Disease Center autopsy cohort (n = 136 subjects). Read More

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https://linkinghub.elsevier.com/retrieve/pii/S09699961183070
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http://dx.doi.org/10.1016/j.nbd.2019.01.013DOI Listing
January 2019
2 Reads

Increased anxiety-like behavior following circuit-specific catecholamine denervation in mice.

Neurobiol Dis 2019 Jan 21;125:55-66. Epub 2019 Jan 21.

Department of Pharmacology, Medical University of Innsbruck, Peter Mayr Strasse 1A, 6020 Innsbruck, Austria. Electronic address:

Parkinson's disease (PD) presents with a constellation of non-motor symptoms, notably increased anxiety, which are currently poorly treated and underrepresented in animal models of the disease. Human post-mortem studies report loss of catecholaminergic neurons in the pre-symptomatic phases of PD when anxiety symptoms emerge, and a large literature from rodent and human studies indicate that catecholamines are important mediators of anxiety via their modulatory effects on limbic regions such as the amygdala. On the basis of these observations, we hypothesized that anxiety in PD could result from an early loss of catecholaminergic inputs to the amygdala and/or other limbic structures. Read More

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http://dx.doi.org/10.1016/j.nbd.2019.01.009DOI Listing
January 2019
5 Reads

The role of pallidum in the neural integrator model of cervical dystonia.

Neurobiol Dis 2019 Jan 22;125:45-54. Epub 2019 Jan 22.

Department of Neurology, Case Western Reserve University, Cleveland, OH, USA; Neurological Institute, University Hospitals, Cleveland, OH, USA; Neurology Service, Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA.. Electronic address:

Dystonia is the third most common movement disorder affecting three million people worldwide. Cervical dystonia is the most common form of dystonia. Despite common prevalence the pathophysiology of cervical dystonia is unclear. Read More

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http://dx.doi.org/10.1016/j.nbd.2019.01.011DOI Listing
January 2019
2 Reads

The α3 and α4 nicotinic acetylcholine receptor (nAChR) subunits in the brainstem medulla of sudden infant death syndrome (SIDS).

Neurobiol Dis 2019 Jan 18;125:23-30. Epub 2019 Jan 18.

The Bosch Institute, Faculty of Health and Medicine, The University of Sydney, NSW 2006, Australia; Central Clinical School of Medicine, Faculty of Health and Medicine, The University of Sydney, NSW 2006, Australia. Electronic address:

SIDS occurs in early infancy and predominantly during a sleep period. Abnormalities in nicotine receptor binding and in the expression of the nicotinic acetylcholine receptor (nAChR) subunits α7 and β2 have been reported in the brainstem of SIDS infants. This study focuses on the α3 and α4 nAChR subunits as α3 is important for early postnatal survival while α4 is crucial for nicotine-elicited antinociception and sleep-wake cycle regulation. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S09699961183062
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http://dx.doi.org/10.1016/j.nbd.2019.01.010DOI Listing
January 2019
8 Reads

Brain insulin response and peripheral metabolic changes in a Tau transgenic mouse model.

Neurobiol Dis 2019 Jan 19;125:14-22. Epub 2019 Jan 19.

Univ. Lille, Inserm, CHU Lille, UMR-S 1172 - JPArc, F-59000 Lille, France; LabEx DISTALZ, F-59000 Lille, France. Electronic address:

Accumulation of hyper-phosphorylated and aggregated Tau proteins is a neuropathological hallmark of Alzheimer's Disease (AD) and Tauopathies. AD patient brains also exhibit insulin resistance. Whereas, under normal physiological conditions insulin signaling in the brain mediates plasticity and memory formation, it can also regulate peripheral energy homeostasis. Read More

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http://dx.doi.org/10.1016/j.nbd.2019.01.008DOI Listing
January 2019
2 Reads

N-Palmitoylethanolamine-oxazoline (PEA-OXA): A new therapeutic strategy to reduce neuroinflammation, oxidative stress associated to vascular dementia in an experimental model of repeated bilateral common carotid arteries occlusion.

Neurobiol Dis 2019 Jan 17;125:77-91. Epub 2019 Jan 17.

Department of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina, Messina, Italy; Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine,Saint Louis, USA. Electronic address:

Aim: Recent studies revealed that pharmacological modulation of NAE-hydrolyzing acid amidase (NAAA) can be achieved with PEA oxazoline (PEA-OXA). Hence, the aim of the present work was to thoroughly evaluate the anti-inflammatory and neuroprotective effects of PEA-OXA in an experimental model of vascular dementia (VaD) induced by bilateral carotid arteries occlusion. At 24 h after VaD induction, animals were orally administered with 10 mg/kg of PEA-OXA daily for 15 days. Read More

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http://dx.doi.org/10.1016/j.nbd.2019.01.007DOI Listing
January 2019
2 Reads

Maternal immune activation-induced PPARγ-dependent dysfunction of microglia associated with neurogenic impairment and aberrant postnatal behaviors in offspring.

Neurobiol Dis 2019 Jan 17;125:1-13. Epub 2019 Jan 17.

School of Life Science and Technology, Center for Informational Biology, University of Electronic Science and Technology of China, Chengdu, Sichuan 610054, China; Department of Histology and Embryology, School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan 646000, China. Electronic address:

Maternal infection during pregnancy is an important factor involved in the pathogenesis of brain disorders in the offspring. Mounting evidence from maternal immune activation (MIA) animals indicates that microglial priming may contribute to neurodevelopmental abnormalities in the offspring. Because peroxisome proliferator-activated receptor gamma (PPARγ) activation exerts neuroprotective effects by regulating neuroinflammatory response, it is a pharmacological target for treating neurogenic disorders. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S09699961183049
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http://dx.doi.org/10.1016/j.nbd.2019.01.005DOI Listing
January 2019
5 Reads

A two-hit story: Seizures and genetic mutation interaction sets phenotype severity in SCN1A epilepsies.

Neurobiol Dis 2019 Jan 17;125:31-44. Epub 2019 Jan 17.

Université Côte d'Azur (UCA), INSERM, CNRS UMR 7275, Institute of Molecular and Cellular Pharmacology (IPMC), Team Pathophysiology of Voltage-Gated Na(+) channels and of Neuronal Excitability, France. Electronic address:

SCN1A (Na1.1 sodium channel) mutations cause Dravet syndrome (DS) and GEFS+ (which is in general milder), and are risk factors in other epilepsies. Phenotypic variability limits precision medicine in epilepsy, and it is important to identify factors that set phenotype severity and their mechanisms. Read More

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http://dx.doi.org/10.1016/j.nbd.2019.01.006DOI Listing
January 2019
3 Reads

Long-term RNAi knockdown of α-synuclein in the adult rat substantia nigra without neurodegeneration.

Neurobiol Dis 2019 Jan 15;125:146-153. Epub 2019 Jan 15.

Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA; Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA, USA; Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA, USA; Geriatric Research, Education and Clinical Center, Pittsburgh VA Healthcare System, Pittsburgh, PA, USA. Electronic address:

α-Synuclein plays a central role in the pathogenesis of Parkinson's disease (PD); interventions that decrease its expression appear neuroprotective in PD models. Successful translation of these observations into effective therapies will be dependent on the safety of suppressing α-synuclein expression in the adult brain. We investigated long-term α-synuclein knockdown in the adult rat CNS. Read More

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http://dx.doi.org/10.1016/j.nbd.2019.01.004DOI Listing
January 2019
5 Reads

Local cortical circuit correlates of altered EEG in the mouse model of Fragile X syndrome.

Neurobiol Dis 2019 Apr 9;124:563-572. Epub 2019 Jan 9.

Department of Basic Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States. Electronic address:

Electroencephalogram (EEG) recordings in Fragile X syndrome (FXS) patients have revealed enhanced sensory responses, enhanced resting "gamma frequency" (30-100 Hz) activity, and a decreased ability for sensory stimuli to modulate cortical activity at gamma frequencies. Similar changes are observed in the FXS model mouse - the Fmr1 knockout. These alterations may become effective biomarkers for diagnosis and treatment of FXS. Read More

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http://dx.doi.org/10.1016/j.nbd.2019.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6371815PMC

Integrative analysis of blood metabolomics and PET brain neuroimaging data for Parkinson's disease.

Neurobiol Dis 2019 Apr 9;124:555-562. Epub 2019 Jan 9.

Clinic for Neurology, University Hospital Giessen and Marburg, Marburg, Germany.

Background: The diagnosis of Parkinson's disease (PD) often remains a clinical challenge. Molecular neuroimaging can facilitate the diagnostic process. The diagnostic potential of metabolomic signatures has recently been recognized. Read More

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http://dx.doi.org/10.1016/j.nbd.2019.01.003DOI Listing
April 2019
2 Reads

Human and rodent temporal lobe epilepsy is characterized by changes in O-GlcNAc homeostasis that can be reversed to dampen epileptiform activity.

Neurobiol Dis 2019 Apr 6;124:531-543. Epub 2019 Jan 6.

Department of Neurobiology, University of Alabama, Birmingham, AL, United States. Electronic address:

Temporal Lobe Epilepsy (TLE) is frequently associated with changes in protein composition and post-translational modifications (PTM) that exacerbate the disorder. O-linked-β-N-acetyl glucosamine (O-GlcNAc) is a PTM occurring at serine/threonine residues that is derived from and closely associated with metabolic substrates. The enzymes O-GlcNActransferase (OGT) and O-GlcNAcase (OGA) mediate the addition and removal, respectively, of the O-GlcNAc modification. Read More

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http://dx.doi.org/10.1016/j.nbd.2019.01.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379093PMC
April 2019
5.078 Impact Factor

Assessment of diets containing curcumin, epigallocatechin-3-gallate, docosahexaenoic acid and α-lipoic acid on amyloid load and inflammation in a male transgenic mouse model of Alzheimer's disease: Are combinations more effective?

Neurobiol Dis 2019 Apr 2;124:505-519. Epub 2019 Jan 2.

School of Medicine, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia; Molecular Medicine Research Group, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia; National Institute of Complementary Medicine, University of Western Sydney, Locked Bag 1797, Penrith, NSW 2751, Australia. Electronic address:

Increasingly, evidence is accumulating pointing at a protective role of a healthy diet at decreasing the risk of Alzheimer's disease. To test the effectiveness of nutritional components, the following food-derived compounds: curcumin alone (curcumin), curcumin combined with (-)epigallocatechin-3-gallate (EGCG), docosahexaenoic acid (DHA) and α-lipoic acid (ALA) (curcumin + EDA), or a combination of EGCG, DHA and ALA (EDA) were assessed in male Tg2576 transgenic mice on amyloid plaque load, amyloid levels (Aβ40/Aβ42, but not oligomers due to tissue limitations), microglial activation and memory using the contextual and cued fear conditioning test. The combination diet EDA, resulted in the strongest reduction of amyloid plaque load in both the cortical (p < . Read More

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http://dx.doi.org/10.1016/j.nbd.2018.11.026DOI Listing

Mutant SOD1 prevents normal functional recovery through enhanced glial activation and loss of motor neuron innervation after peripheral nerve injury.

Neurobiol Dis 2019 Apr 27;124:469-478. Epub 2018 Dec 27.

Department of Neurology and Rehabilitation, Graduate Program in Neuroscience, University of Illinois at Chicago, 912 S. Wood Street, Chicago, IL 60612, USA. Electronic address:

Background: Amyotrophic lateral sclerosis (ALS) is poorly understood with no effective therapeutics. One long entertained observation is that ALS may be precipitated focally by nerve injury. Many patients with ALS are athletes or veterans, and some have suffered nerve injuries at the site where ALS first presents. Read More

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http://dx.doi.org/10.1016/j.nbd.2018.12.020DOI Listing

Pridopidine stabilizes mushroom spines in mouse models of Alzheimer's disease by acting on the sigma-1 receptor.

Neurobiol Dis 2019 Apr 27;124:489-504. Epub 2018 Dec 27.

Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Laboratory of Molecular Neurodegeneration, Peter the Great St. Petersburg Polytechnic University, St. Petersburg, Russia. Electronic address:

There is evidence that cognitive decline in Alzheimer's disease (AD) results from deficiencies in synaptic communication (e.g., loss of mushroom-shaped 'memory spines') and neurodegenerative processes. Read More

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http://dx.doi.org/10.1016/j.nbd.2018.12.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363865PMC
April 2019
3 Reads

Decreased circulating ErbB4 ectodomain fragments as a read-out of impaired signaling function in amyotrophic lateral sclerosis.

Neurobiol Dis 2019 Apr 27;124:428-438. Epub 2018 Dec 27.

Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Sant Joan d'Alacant, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain. Electronic address:

ErbB4 is a transmembrane receptor tyrosine kinase that binds to neuregulins to activate signaling. Proteolytic cleavage of ErbB4 results in release of soluble fragments of ErbB4 into the interstitial fluid. Disruption of the neuregulin-ErbB4 pathway has been suggested to be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). Read More

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http://dx.doi.org/10.1016/j.nbd.2018.12.021DOI Listing
April 2019
2 Reads

Rho-kinase inhibition has antidepressant-like efficacy and expedites dendritic spine pruning in adolescent mice.

Neurobiol Dis 2019 Apr 26;124:520-530. Epub 2018 Dec 26.

Molecular and Systems Pharmacology, Emory University, Atlanta, GA, United States; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, United States; Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States; Graduate Program in Neuroscience, Emory University, Atlanta, GA, United States; Department of Psychiatry, Emory University School of Medicine, Atlanta, GA, United States. Electronic address:

Adolescence represents a critical period of neurodevelopment, defined by structural and synaptic pruning within the prefrontal cortex. While characteristic of typical development, this structural instability may open a window of vulnerability to developing neuropsychiatric disorders, including depression. Thus, therapeutic interventions that support or expedite neural remodeling in adolescence may be advantageous. Read More

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http://dx.doi.org/10.1016/j.nbd.2018.12.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365018PMC

Low cerebral blood flow is a non-invasive biomarker of neuroinflammation after repetitive mild traumatic brain injury.

Neurobiol Dis 2019 Apr 25;124:544-554. Epub 2018 Dec 25.

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, USA; Department of Pediatrics, School of Medicine, Emory University, USA. Electronic address:

Previous work has shown that non-invasive optical measurement of low cerebral blood flow (CBF) is an acute biomarker of poor long-term cognitive outcome after repetitive mild traumatic brain injury (rmTBI). Herein, we explore the relationship between acute cerebral blood flow and underlying neuroinflammation. Specifically, because neuroinflammation is a driver of secondary injury after TBI, we hypothesized that both glial activation and inflammatory signaling are associated with acute CBF and, by extension, with long-term cognitive outcome after rmTBI. Read More

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http://dx.doi.org/10.1016/j.nbd.2018.12.018DOI Listing
April 2019
5.078 Impact Factor

Diving responses elicited by nasopharyngeal irrigation mimic seizure-associated central apneic episodes in a rat model.

Neurobiol Dis 2019 Apr 25;124:408-415. Epub 2018 Dec 25.

Departments of Physiology & Pharmacology, SUNY Downstate Medical Center, Brooklyn, NY, USA; Neurology, SUNY Downstate Medical Center, Brooklyn, NY, USA. Electronic address:

The spread of epileptic seizure activity to brainstem respiratory and autonomic regions can elicit episodes of obstructive apnea and of central apnea with significant oxygen desaturation and bradycardia. Previously, we argued that central apneic events were not consequences of respiratory or autonomic activity failure, but rather an active brainstem behavior equivalent to the diving response resulting from seizure spread. To test the similarities of spontaneous seizure-associated central apneic episodes to evoked diving responses, we used nasopharyngeal irrigation with either cold water or mist for 10 or 60 s to elicit the diving response in urethane-anesthetized animals with or without kainic acid-induced seizure activity. Read More

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http://dx.doi.org/10.1016/j.nbd.2018.12.019DOI Listing
April 2019
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Cell injury and receptor expression in the epileptic human amygdala.

Neurobiol Dis 2019 Apr 24;124:416-427. Epub 2018 Dec 24.

Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran; Department of Neurology with Institute of Translational Neurology, Westfälische Wilhelms-Universität Münster, Germany; Department of Neurosurgery, Westfälische Wilhelms-Universität Münster, Germany; Epilepsy research center, Westfälische Wilhelms-Universität Münster, Germany; Department of Neuroscience, Mashhad University of Medical Sciences, Iran. Electronic address:

Neuropathological findings in the amygdala obtained from patients with mesial temporal lobe epilepsy (MTLE) indicate varying degrees of histopathological alterations, such as neuronal loss and gliosis. The mechanisms underlying cellular damage in the amygdala of patients with MTLE have not been fully elucidated. In the present study, we assess cellular damage, determine the receptor expression of major inhibitory and excitatory neurotransmitters, and evaluate the correlation between the expression of various receptors and cell damage in the basolateral complex and the centromedial areas in the amygdala specimens resected during brain surgery on 30 patients with medically intractable MTLE. Read More

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http://dx.doi.org/10.1016/j.nbd.2018.12.017DOI Listing
April 2019
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Brain proteome changes in female Brd1 mice unmask dendritic spine pathology and show enrichment for schizophrenia risk.

Neurobiol Dis 2019 Apr 24;124:479-488. Epub 2018 Dec 24.

The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark; Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark; Department of Biomedicine, Aarhus University, Aarhus, Denmark.

Genetic and molecular studies have implicated the Bromodomain containing 1 (BRD1) gene in the pathogenesis of schizophrenia and bipolar disorder. Accordingly, mice heterozygous for a targeted deletion of Brd1 (Brd1 mice) show behavioral phenotypes with broad translational relevance to psychiatric disorders. BRD1 encodes a scaffold protein that affects the expression of many genes through modulation of histone acetylation. Read More

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http://dx.doi.org/10.1016/j.nbd.2018.12.011DOI Listing
April 2019
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High-frequency oscillations and focal seizures in epileptic rodents.

Neurobiol Dis 2019 Apr 24;124:396-407. Epub 2018 Dec 24.

Montreal Neurological Institute, Canada; Departments of Neurology & Neurosurgery, and of Physiology, McGill University, Montréal, H3A 2B4 Québec, Canada; Department of Experimental Medicine, Facoltà di Medicina e Odontoiatria, Sapienza University of Rome, 00185 Roma, Italy.

High-pass filtering (> 80 Hz) of EEG signals has enabled neuroscientists to analyze high-frequency oscillations (HFOs; i.e., ripples: 80-200 Hz and fast ripples: 250-500 Hz) in epileptic patients presenting with focal seizures and in animal models mimicking this condition. Read More

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http://dx.doi.org/10.1016/j.nbd.2018.12.016DOI Listing

Changes of dimension of EEG/ECoG nonlinear dynamics predict epileptogenesis and therapy outcomes.

Neurobiol Dis 2019 Apr 24;124:373-378. Epub 2018 Dec 24.

Department of Neuroscience, Mario Negri Institute for Pharmacological Research IRCCS, Milano, Italy.

The lack of early biomarkers of epileptogenesis precludes a sound prediction of epilepsy development after acute brain injuries and of the natural course of the disease thus impairing the development of antiepileptogenic treatments. We investigated whether the dimensional changes of nonlinear dynamics in EEG/ECoG signals, that were recorded in the early aftermath of different epileptogenic injuries, provide a measure to be exploited as a sensitive prognostic and predictive biomarker for epilepsy. Using three different models of epilepsy in two rodent species, we report a common and significant decrease of nonlinear dynamics dimension in EEG/ECoG tracings during early epileptogenesis. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S09699961183065
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http://dx.doi.org/10.1016/j.nbd.2018.12.014DOI Listing
April 2019
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Neural correlates of cognitive deficits across developmental phases of schizophrenia.

Neurobiol Dis 2018 Dec 21. Epub 2018 Dec 21.

Massachusetts Mental Health Center, Public Psychiatry Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Schizophrenia is associated with cognitive deficits across all stages of the illness (i.e., high risk, first episode, early and chronic phases). Read More

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http://dx.doi.org/10.1016/j.nbd.2018.12.013DOI Listing
December 2018

Chronic stress-induced gut dysfunction exacerbates Parkinson's disease phenotype and pathology in a rotenone-induced mouse model of Parkinson's disease.

Neurobiol Dis 2018 Dec 21. Epub 2018 Dec 21.

Department of Internal Medicine, Division of Digestive Diseases, Rush University Medical Center, Chicago, IL, USA; Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands. Electronic address:

Recent evidence provides support for involvement of the microbiota-gut-brain axis in Parkinson's disease (PD) pathogenesis. We propose that a pro-inflammatory intestinal milieu, due to intestinal hyper-permeability and/or microbial dysbiosis, initiates or exacerbates PD pathogenesis. One factor that can cause intestinal hyper-permeability and dysbiosis is chronic stress which has been shown to accelerate neuronal degeneration and motor deficits in Parkinsonism rodent models. Read More

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http://dx.doi.org/10.1016/j.nbd.2018.12.012DOI Listing
December 2018
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Cinnamic acid activates PPARα to stimulate Lysosomal biogenesis and lower Amyloid plaque pathology in an Alzheimer's disease mouse model.

Neurobiol Dis 2019 Apr 19;124:379-395. Epub 2018 Dec 19.

Department of Neurological Sciences, Rush University Medical Center, Chicago, USA; Division of Research and Development, Jesse Brown Veterans Affairs Medical Center, Chicago, USA. Electronic address:

The response of the lysosomes, the waste clearance machinery of the cell, to different environmental stimuli is coordinated by a gene network with a master regulator Transcription factor EB (TFEB) at the core. Disruption of multiple facets of the lysosomal and autophagic network has been linked to various neurodegenerative and lysosomal storage disorders, making TFEB an attractive therapeutic target to rescue or augment lysosomal function under pathological scenario. In this study, we demonstrate that cinnamic acid, a naturally occurring plant-based product, induces lysosomal biogenesis in mouse primary brain cells via upregulation of TFEB. Read More

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http://dx.doi.org/10.1016/j.nbd.2018.12.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6382282PMC
April 2019
1 Read

Activation of enkephalinergic (Enk) interneurons in the central amygdala (CeA) buffers the behavioral effects of persistent pain.

Neurobiol Dis 2019 Apr 17;124:364-372. Epub 2018 Dec 17.

Department of Physiology and Biophysics, Chicago Medical School Rosalind Franklin University of Medicine and Science, 3333 Green Bay Rd., North Chicago, IL 60064, United States. Electronic address:

Enk neurons in CeA modulate the activity of the amygdala projection neurons and it is very likely that changes of Enk signaling cause the heightened anxiety that accompanies chronic pain. We use chemogenetics and transgenic mice to investigate the effects of acute and continuous activation of the amygdala Enk neurons on persistent pain and anxiodepressive-like behavior in mice. Enk-cre mice were injected bilaterally into the CeA with cre-activated AAV-DREADD/Gq/mCherry, while neuropathic pain was induced by sciatic nerve constriction. Read More

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http://dx.doi.org/10.1016/j.nbd.2018.12.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363838PMC
April 2019
1 Read

A multiomic approach to characterize the temporal sequence in Alzheimer's disease-related pathology.

Neurobiol Dis 2019 Apr 15;124:454-468. Epub 2018 Dec 15.

Institute of Biomedicine, University of Eastern Finland, Kuopio 70210, Finland. Electronic address:

No single-omic approach completely elucidates the multitude of alterations taking place in Alzheimer's disease (AD). Here, we coupled transcriptomic and phosphoproteomic approaches to determine the temporal sequence of changes in mRNA, protein, and phosphopeptide expression levels from human temporal cortical samples, with varying degree of AD-related pathology. This approach highlighted fluctuation in synaptic and mitochondrial function as the earliest pathological events in brain samples with AD-related pathology. Read More

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http://dx.doi.org/10.1016/j.nbd.2018.12.009DOI Listing
April 2019
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Following spinal cord injury, PDE4B drives an acute, local inflammatory response and a chronic, systemic response exacerbated by gut dysbiosis and endotoxemia.

Neurobiol Dis 2019 Apr 14;124:353-363. Epub 2018 Dec 14.

Kentucky Spinal Cord Injury Research Center, University of Louisville, School of Medicine, 511 S. Floyd St., MDR 616, Louisville, KY 40202, USA; Department of Neurological Surgery, University of Louisville, School of Medicine, 511 S. Floyd St., MDR 616, Louisville, KY 40202, USA; Department of Anatomical Science & Neurobiology, University of Louisville, School of Medicine, 511 S. Floyd St., MDR 616, Louisville, KY 40202, USA. Electronic address:

Emerging evidence links changes in the gut microbiome and intestinal barrier function to alterations in CNS function. We examined the role of endotoxin-responsive, cAMP-specific, Pde4 subfamily b (Pde4b) enzyme in gut dysbiosis induced neuro-inflammation and white matter loss following spinal cord injury (SCI). Using a thoracic contusion model in C57Bl/6 wild type female mice, SCI led to significant shifts in the gut bacterial community including an increase in the phylum Proteobacteria, which consists of endotoxin-harboring, gram-negative bacteria. Read More

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http://dx.doi.org/10.1016/j.nbd.2018.12.008DOI Listing
April 2019
1 Read