Ganglioside GM3 synthase (α-2,3-sialyltransferase, ST3GAL5, GM3S) is a key enzyme involved in the biosynthesis of gangliosides. ST3GAL5 deficiency causes an absence of GM3 and all downstream biosynthetic derivatives. The affected individuals manifest deafness, severe irritability, intractable seizures, and profound intellectual disability. To investigate whether deficiency of GM3 is involved in seizure

The p75 neurotrophin receptor (p75NTR) can regulate multiple cellular functions including proliferation, survival, and apoptotic cell death. The p75NTR is widely expressed in the developing brain and is downregulated as the nervous system matures, with only a few neuronal subpopulations retaining expression into adulthood. However, p75NTR expression is induced following damage to the adult brain, including

Cognitive dysfunction is one of the most severe nonmotor symptoms of nigrostriatal impairment. This occurs as a result of profound functional and morphological changes of different neuronal circuits, including modifications in the plasticity and architecture of hippocampal synapses. Such alterations can be implicated in the genesis and progression of dementia associated with neurodegenerative diseases

Microglia, the resident immune cells of the central nervous system, are not a homogeneous population; their morphology, molecular profile, and even their ultrastructure greatly vary from one cell to another. Recent advances in the field of neuroimmunology have helped to demystify the enigma that currently surrounds microglial heterogeneity. Indeed, numerous microglial subtypes have been discovered

The deposition of amyloid-β peptides in the form of extracellular plaques and neuronal degeneration belong to the hallmark features of Alzheimer's disease (AD). In addition, impaired calcium homeostasis and altered levels in calcium-binding proteins seem to be associated with the disease process. In this study, calretinin- (CR) and parvalbumin- (PV) positive gamma-aminobutyric acid-producing (GABAergic)

Nuclear-distribution element-like 1 (NDEL1) is associated with the proliferation and migration of neurons. Vascular endothelial growth factor (VEGF) in combination with VEGF receptor-2 (VEGFR-2) regulates the proliferation and migration of neurons. This study was performed to explore undefined alterations in the expression levels of NDEL1 and VEGF/VEGFR-2 within the hippocampus after status epilepticus

There is a critical need for understanding the progression of neuropathology in blast-induced traumatic brain injury using valid animal models to develop diagnostic approaches. In the present study, we used diffusion imaging and magnetic resonance (MR) morphometry to characterize axonal injury in white matter structures of the rat brain following a blast applied via blast tube to one side of the brain

Late-onset Alzheimer’s disease (LOAD) is a long-enduring neurodegenerative disease (Jack et al., 2018) that progresses for decades before the symptoms of cognitive decline and loss of executive function are measurable.

Mild traumatic brain injury (mTBI) is the most common (>80% cases) type of TBI within the military and civilian populations and is a major cause of disability and functional impairment. Epidemiological studies have reported that individuals exposed to a history of TBI are more susceptible to developing sporadic age-related neurodegenerative conditions in later life (Gedye et al., 1989; Mortimer et al

The ventromedial hypothalamic nucleus (VMN) integrates nutrient and other cues to control glucostasis (Watts and Donovan, 2010; Donovan and Watts, 2014). VMN metabolic-sensory neurons adjust synaptic firing to supply a dynamic readout of neuroenergetic state (Oomura et al., 1969; Ashford et al., 1990; Silver and Erecińska, 1998). Characterized effector transmitters of energy insufficiency within the

Traumatic brain injury (TBI) is known as a “silent epidemic” (Simon et al., 2017). Annually, approximately 54 to 60 million people suffer from TBI worldwide (Bazarian et al., 2018). Survivors of TBI commonly live with neurocognitive deficits and physical disability and increased risk of neurodegenerative disease in the long term (Pattinson and Gill, 2018). Unfortunately, no drug has been approved in

Traumatic brain injury (TBI) affects more than 1.5 million people in the United States each year with a mortality rate near or above 50,000 per year (Coronado et al., 2011; Thurman et al., 1999). TBI causes a prolonged secondary inflammatory response within the central nervous system (CNS) that leads to neurological deficits, both motor and cognitive, beyond that caused by the primary injury (Ramlackhansingh

Reactive oxygen species (ROS) serve as critical intracellular signaling molecules but in excess can cause oxidative stress and damage organelles and macromolecules, eventually leading to cell death (Zuo et al., 2015). Increased ROS production and oxidative stress have been implicated in the pathogenesis of numerous neurodegenerative conditions, including, among others, Alzheimer’s disease (AD; Behl

Physical exercise has been associated with enhanced memory formation and consolidation (Fernandes et al., 2016). With regard to individuals with mild cognitive impairment (MCI), two review articles reveal inconclusive results with regard to beneficial effects of exercise on cognitive function (Gates et al., 2013; Ohman et al., 2014), while other two meta-analysis studies show aerobic exercise significantly

Carcinogenesis is a complex and multi-etiological process resulting in the accumulation of genetic alterations primarily in genes involved in the regulation of signaling pathways relevant to the control of cell growth and division (reviewed in Hanahan and Weinberg, 2011). Neoplastic processes include a number of typical characteristics such as sustained proliferative activation, growth suppressor evasion

Skeletal muscle loss and dysfunction are found in Huntington’s disease (HD), which is a progressive neurodegenerative disorder caused by an autosomal dominant condition leading to motor, cognitive, and psychiatric impairment. In 1993, the Huntington’s Disease Collaborative Research Group identified a mutation in the short arm of Chromosome 4, an unstable expansion in the number of CAG repeats in the

Alzheimer’s disease (AD) is the most common form of dementia. There is accumulating evidence that in addition to genetics, other lifestyle and environmental factors may have a share in the individual risk of getting AD, which opens new opportunities for prevention (Mattson, 2015). Risk factors include diabetes mellitus, midlife obesity and hypertension, smoking, depression and dyslipidemia (Mayeux

We previously showed that clinical scores in the myelin oligodendrocyte glycoprotein (MOG)35–55 peptide-induced experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS) were significantly reduced by administration of lanthionine ketimine ethyl ester (LKE), accompanied by reductions in axonal damage in spinal cord and optic nerve (Dupree et al., 2015). LKE is a derivatized form

We previously reported that ganglioside GD3 is the predominant species in neural stem cells (NSCs) and reduced postnatal NSC pools are observed in both the subventricular zone and dentate gyrus (DG) of GD3-synthase knockout (GD3S-KO) mouse brains. Specifically, deficiency of GD3 in GD3S-KO animals revealed a dramatic reduction in cellularity in the DG of the hippocampus of the developing mouse brain

Erythropoietin (EPO) is a 30-kDa molecular weight glycoprotein of 165 amino acids, coded by the EPO gene, located on Chromosome 7 (Law et al., 1986). EPO presents one small O-linked glycan and three tetra-antennary N-linked polysaccharide units, fundamental for its secretion, molecular stability, and binding to its receptor, erythropoietin receptor (EPOR; Tsuda et al., 1988). EPO is a type I cytokine

Elevated blood levels of the amino acid homocysteine, termed hyperhomocysteinemia (HHcy), is a risk factor for cognitive impairment and dementia (Smith et al., 2018). Strikingly, the population attributable risk of Alzheimer’s disease (AD) due to HHcy is estimated to be as high as 31% (Van Dam & Van Gool, 2009; Smith et al., 2018), and it follows that successful treatment of this condition may significantly

Increased attention to the role of glial activities in neural functions and diseases has drawn the participation of more than 180 experts who engaged in glial cell research to the 2019 Academic Annual Meeting and the Frontier Seminar on “Glial Cell Function and Disease” held in Nantong, China from May 24 to 26. The meeting was organized by Drs. Yong-Jing Gao and Jia-Wei Zhou of the Chinese Society

Zika virus (ZIKV) is an arthropod-borne virus member of the Flaviviridae family, Flavivirus genus. The family comprises viruses with positive-sense RNA genomes, and other family members include important human pathogens including Yellow Fever Virus (YFV), Dengue Virus (DENV), West Nile Virus (WNV), Japanese Encephalitis Virus (JEV), and Spondweni Virus (SPOV). Although ZIKV was repeatedly isolated

Huntington’s disease (HD) is a progressive neurodegenerative disorder characterized by symptoms that include involuntary movement of the body, loss of cognitive function, psychiatric disorders, and inevitable death (Ehrnhoefer et al., 2009, Labbadia and Morimoto, 2013). HD is an autosomal dominant disease caused by poly-glutamine expansion in a protein named huntingtin (Htt), leading to aggregate formation

Brain development is a very complex, dynamic, and multistage process that involves precisely orchestrated sequence of cellular and molecular events (Silbereis et al., 2016). This development begins within weeks of conception (∼third gestational week) and continues through the adolescence (Stiles and Jernigan, 2010). Many controlled morphogenesis processes such as cell division, differentiation, migration

The glutamatergic synapse, referred to as the tripartite synapse, involves three elements: presynaptic neurons, postsynaptic neurons, and astrocytes. There are several different synaptic components expressed on both neurons and astrocytes in the glutamate synapse, as summarized in Table 1. These components include two types of glutamate receptors that exist on these synaptic elements: metabotropic

In the United States, the annual incidence of nonmilitary-related traumatic brain injury (TBI) is approximately 1.7 million, of which 327,000 are hospitalized and 52,000 die (Faul et al., 2010). Juvenile TBI (jTBI), which is the leading cause of death and disability in children and adolescents, is an important concern because the population group most affected (emergency department visit, hospitalization

Cerebrospinal fluid (CSF) biomarkers are widely used in the diagnosis of dementia. Even though there is a causal correlation between apolipoprotein E ( APOE) genotype and amyloid-beta (Aβ), the determination of APOE is currently not supported by national or international guidelines. We compared parallel measured CSF biomarkers of two independent laboratories from 126 patients who underwent clinical

In the supraoptic nucleus (SON), the incidence of dye coupling among oxytocin (OT) neurons increases significantly in nursing mothers. However, the type(s) of connexin (Cx) involved is(are) unknown. In this study, we specifically investigated whether Cx36 plays a functional role in the coupling between OT neurons in the SON of lactating rats. In this brain region, Cx36 was mainly coimmunostained with

BACKGROUND Frontotemporal lobar degeneration (FTLD) is the third most common dementing neurodegenerative disease with nearly 80% having no known etiology. OBJECTIVE Growing evidence that neurodegeneration can be linked to dysregulated metabolism prompted us to measure a panel of trophic factors, receptors, and molecules that modulate brain metabolic function in FTLD. METHODS Postmortem frontal (Brodmann's

During Wallerian degeneration, Schwann cells lose their characteristic of myelinating axons and shift into the state of developmental promyelinating cells. This recharacterized Schwann cell guides newly regrowing axons to their destination and remyelinates reinnervated axons. This Schwann cell dynamics during Wallerian degeneration is associated with oxidative events. Heme oxygenases (HOs) are involved

In humans, homozygous mutations in the TPP1 gene results in loss of tripeptidyl peptidase 1 (TPP1) enzymatic activity, leading to late infantile neuronal ceroid lipofuscinoses disease. Using a mouse model that targets the Tpp1 gene and recapitulates the pathology and clinical features of the human disease, we analyzed end-stage (4 months) transcriptional changes associated with lack of TPP1 activity

ATP- and adenosine-mediated signaling are prominent types of glia-glia and glia-neuron interaction, with an imbalance of ATP/adenosine ratio leading to altered states of excitability, as seen in epileptic seizures. Pannexin1 (Panx1), a member of the gap junction family, is an ATP release channel that is expressed in astrocytes and neurons. Previous studies provided evidence supporting a role for purinergic-mediated

Phosphodiesterases (PDEs) have previously been implicated in oligodendrocyte maturation and myelination of central nervous system axons. Sildenafil citrate is a phosphodiesterase inhibitor known to block PDE5, which also reduces inflammation in the experimental autoimmune encephalomyelitis demyelinating model. To find out whether this inhibitor might exert beneficial effects on central nervous system

There is intense interest and effort toward regenerating the brain after severe injury. Stem cell transplantation after insult to the central nervous system has been regarded as the most promising approach for repair; however, engrafting cells alone might not be sufficient for effective regeneration. In this study, we have compared neural progenitors (NPs) from the fetal ventricular zone (VZ), the

A high proportion of adults who sustain a concussion identify changes in their sleep during the acute stage, typically reporting an increased need for sleep or nonrestful sleep. Our understanding of sleep following concussion is less well understood within a pediatric population. In this study, we investigated the trajectory of sleep and daytime sleepiness in a prospective cohort of 40 children and

Protein aggregation and accumulation are common pathological hallmarks in neurodegenerative diseases. To efficiently clear and eliminate such aggregation becomes an important cellular strategy for cell survival. Lewy bodies inclusion and aggregation of α-Synuclein (α-Syn) during the pathogenesis of Parkinson's disease (PD) serve as a good example and are potentially linked to other pathological PD

Levodopa (L-DOPA) is still the most effective drug for the treatment of Parkinson's disease (PD). However, the long-term therapy often triggers L-DOPA-induced dyskinesia (LID). Metabotropic glutamate receptor type 5 (mGluR5) is abundant in the basal ganglia, and its inhibition is thought to modulate postsynaptic excitatory synaptic transmission and glutamate hyperactivity in PD and LID. In this report

Hyperammonemia associated with overt hepatic encephalopathy (OHE) causes excitotoxic neuronal death through activation of the cytochrome C (CytC)-mediated mitochondria-dependent apoptotic pathway. We tested the therapeutic effect of nortriptyline (NT), a mitochondrial permeability transition pore (mPTP) blocker that can possibly inhibit mitochondrial CytC efflux to the cytosol on in vivo and in vitro

Charcot-Marie-Tooth Disorder Type 4B (CMT4B) is a demyelinating peripheral neuropathy caused by mutations in myotubularin-related (MTMR) proteins 2, 13, or 5 (CMT4B1/2/3), which regulate phosphoinositide turnover and endosomal trafficking. Although mouse models of CMT4B2 exist, an in vitro model would make possible pharmacological and reverse genetic experiments needed to clarify the role of MTMR13

Fragile X syndrome (FXS) is a neurodevelopmental disorder that causes intellectual disability. It is a leading known genetic cause of autism. In addition to cognitive, social, and communication deficits, humans with FXS demonstrate abnormal sensory processing including sensory hypersensitivity. Sensory hypersensitivity commonly manifests as auditory, tactile, or visual defensiveness or avoidance. Clinical

Continuous exposure to aerosolized fine (particle size ≤2.5 µm) and ultrafine (particle size ≤0.1 µm) particulates can trigger innate inflammatory responses in the lung and brain depending on particle composition. Most studies of manmade toxicants use inhalation exposure routes, whereas most studies of allergens use soluble solutions administered via intranasal or injection routes. Here, we tested

Fluoro-Jade is a fluorescein-derived fluorochrome which specifically binds to damaged neurons. Due to this characteristic, it is commonly used for the histochemical detection and quantification of neurodegeneration in mounted brain sections. Here, we describe an alternative and simpler histochemistry protocol based on the use of free-floating brain sections. For this purpose, we have used brain slices

An estimated 5.3 million Americans are living with a disability from a traumatic brain injury (TBI). There is emerging evidence of the detrimental effects from repeated mild TBIs (rmTBIs). rmTBI manifests its own unique set of behavioral and neuropathological changes. A subset of individuals exposed to rmTBI develop permanent behavioral and pathological consequences, defined postmortem as chronic traumatic

Parkinson's disease (PD) is a neurodegenerative movement disorder involving the selective loss of dopamine-producing neurons in the substantia nigra (SN). Differences in disease presentation, prevalence, and age of onset have been reported between males and females with PD. The content and composition of the major glycosphingolipids, phospholipids, and cholesterol were evaluated in the SN from 12 PD

C-type lectin domain family 18 member B (CLEC18B), encoding a superfamily of CLEC, has been found to be expressed in some of cancer cells, which possibly indicates it associated with cancer. However, the defined functional characterizations of CLEC18B in glioblastoma multiforme (GBM) progression still remain unclear. To this end, clinical relevance of CLEC18B expression with GBM patients' prognosis

Parkinson disease (PD) is the second most common neurodegenerative movement disorder. Pharmacological animal models are invaluable tools to study the pathological mechanisms of PD. Currently, invertebrate and vertebrate animal models have been developed by using several main neurotoxins, such as 6-hydroxydopamine, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, paraquat, and rotenone. These models achieve

The compact myelin sheath is important for axonal function, and its loss can lead to neuronal cell death and irreversible functional deficits. Myelin is vulnerable to a variety of metabolic, toxic, and autoimmune insults. In diseases like multiple sclerosis, there is currently no therapy to stop myelin loss, underscoring the need for neuroprotective and remyelinating therapies. Noninvasive, robust

Oxidative stress plays an important role in the onset and progression of Parkinson disease. Although released dopamine at the synaptic terminal is mostly reabsorbed by dopaminergic neurons, some dopamine is presumably taken up by astroglia. This study examined the dopamine-induced astroglial protective function through the activation of the pentose-phosphate pathway (PPP) to reduce reactive oxygen

Mild traumatic brain injury (mTBI) in children is a common and serious public health problem. Traditional neuroimaging findings in children who sustain mTBI are often normal, putting them at risk for repeated mTBI (rmTBI). There is a need for more sensitive imaging techniques capable of detecting subtle neurophysiological alterations after injury. We examined neurochemical and white matter changes

Nodes of Ranvier and associated paranodal and juxtaparanodal domains along myelinated axons are essential for normal function of the peripheral and central nervous systems. Disruption of these domains as well as increases in the reactive carbonyl species methylglyoxal are implicated as a pathophysiology common to a wide variety of neurological diseases. Here, using an ex vivo nerve exposure model,

Sports-related concussion in youth is a major public health issue. Evaluating the diffuse and often subtle changes in structure and function that occur in the brain, particularly in this population, remains a significant challenge. The goal of this pilot study was to evaluate the relationship between the intrinsic dynamics of the brain using resting-state functional magnetic resonance imaging (rs-fMRI)

Lavezzi, A. M., Ferrero, S., Roncati, L., Piscioli, F., Matturri, L. & Pusiol, T. (2017). Nicotinic receptor abnormalities in the cerebellar cortex of sudden unexplained fetal and infant death victims-possible correlation with maternal smoking. ASN Neuro, 9, 1-10. DOI: 10.1177/1759091417720582 In figure 4, one of the labels mentioned at the bottom of graph is incorrect. Instead of "BDNF-index classes"

Glioblastoma multiforme (GBM) is the most common and malignant of the primary adult brain cancers. Ultrastructural and biochemical evidence shows that GBM cells exhibit mitochondrial abnormalities incompatible with energy production through oxidative phosphorylation (OxPhos). Under such conditions, the mitochondrial F0-F1 ATP synthase operates in reverse at the expense of ATP hydrolysis to maintain

Iron deficiency (ID) affects more than three billion people worldwide making it the most common micronutrient deficiency. ID is most prevalent during gestation and early life, which is of particular concern since its impact on the developing central nervous system is associated with an increased risk of a wide range of different psychiatric disorders later in life. The cause for this association is

The axon initial segment (AIS), the domain responsible for action potential initiation and maintenance of neuronal polarity, is targeted for disruption in a variety of central nervous system pathological insults. Previous work in our laboratory implicates oxidative stress as a potential mediator of structural AIS alterations in two separate mouse models of central nervous system inflammation, as these

High plasma levels of homocysteine, termed hyperhomocysteinemia, are a risk factor for vascular cognitive impairment and dementia, which is the second leading cause of dementia. While hyperhomocysteinemia induces microhemorrhages and cognitive decline in mice, the specific effect of hyperhomocysteinemia on each cell type remains unknown. We took separate cultures of astrocytes, microglia, endothelial

Tissue inhibitor of metalloproteinase-3 (TIMP-3) inhibits the activities of various metalloproteinases including matrix metalloproteinases and ADAM family proteins. In the peripheral nervous system, ADAM17, also known as TNF-α converting enzyme (TACE), cleaves the extracellular domain of Nrg1 type III, an axonal growth factor that is essential for Schwann cell myelination. The processing by ADAM17

Mitogen-activated protein kinase (MAPK) signaling has been implicated in a wide range of neuronal processes, including development, plasticity, and viability. One of the principal downstream targets of both the extracellular signal-regulated kinase/MAPK pathway and the p38 MAPK pathway is Mitogen- and Stress-activated protein Kinase 1 (MSK1). Here, we sought to understand the role that MSK1 plays in

The cuprizone model is a well-established and investigated paradigm to study demyelination and remyelination in rodents. Cuprizone is usually administrated by mixing in the powdered or pelleted rodent chow. However, since cuprizone is sensitive to the environment and the consumption of it varies between different animals, the major issue is the discrepancy in demyelination of the animals. This study