Although all cells contain iron, most histochemical methods fail to reveal the presence of iron within many cells of the central nervous system (CNS), particularly neurons. Previously, a sensitive method was developed that limited the extraction of iron in paraffin sections, and this method revealed staining within neurons. However, the staining was often too robust making it difficult to discern discrete

The mammalian circadian clock at the hypothalamic suprachiasmatic nuclei (SCN) entrains biological rhythms to the 24-h cyclic environment, by encoding light-dark transitions in SCN neurons. Light pulses induce phase shifts in the clock and in circadian rhythms; photic signaling for circadian phase advances involves a nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/cGMP-dependent protein kinase

Comorbid post-traumatic stress disorder with traumatic brain injury (TBI) produce more severe affective and cognitive deficits than PTSD or TBI alone. Both PTSD and TBI produce long-lasting neuroinflammation, which may be a key underlying mechanism of the deficits observed in co-morbid TBI/PTSD. We developed a model of co-morbid TBI/PTSD by combining the closed head (CHI) model of TBI with the chronic

Alzheimer’s disease is a neuropathological condition with abnormal accumulation of extracellular Amyloid-β plaques and intracellular neurofibrillary tangles of Microtubule-associated protein Tau (Tau) in the brain. In pathological conditions, Tau undergoes post-translational modifications such as hyperphosphorylation by the activity of cellular kinases, which eventually leads to protein aggregation

Walch, E., Murphy, T. R., Cuvelier, N., Aldoghmi, M., Morozova, C., Donohue, J., Young, G., Samant, A., Garcia, S., Alvarez, C., Bilas, A., Davila, D., Binder, D. K., & Fiacco, T. A. (2020). Astrocyte-Selective Volume Increase in Elevated Extracellular Potassium Conditions Is Mediated by the Na+/K+ ATPase and Occurs Independently of Aquaporin 4. ASN Neuro. https://doi.org/10.1177/1759091420967152

While seizure disorders are more prevalent among multiple sclerosis (MS) patients than the population overall and prognosticate earlier death & disability, their etiology remains unclear. Translational data indicate perturbed expression of astrocytic molecules contributing to homeostatic neuronal excitability, including water channels (AQP4) and synaptic glutamate transporters (EAAT2), in a mouse model

Elevated extracellular potassium chloride is widely used to achieve membrane depolarization of cultured neurons. This technique has illuminated mechanisms of calcium influx through L-type voltage sensitive calcium channels, activity-regulated signaling, downstream transcriptional events, and many other intracellular responses to depolarization. However, there is enormous variability in these treatments

The ERK1/2 signaling pathway promotes myelin wrapping during development and remyelination, and sustained ERK1/2 activation in the oligodendrocyte (OL) lineage results in hypermyelination of the CNS. We therefore hypothesized that increased ERK1/2 signaling in the OL lineage would 1) protect against immune-mediated demyelination due to increased baseline myelin thickness and/or 2) promote enhanced

Norepinephrine (NE) control of hypothalamic gluco-regulation involves astrocyte-derived energy fuel supply. In male rats, exogenous NE regulates astrocyte glycogen metabolic enzyme expression in vivo through 5’-AMP-activated protein kinase (AMPK)-dependent mechanisms. Current research utilized a rat hypothalamic astrocyte primary culture model to investigate the premise that NE imposes sex-specific

Astrocytes and neurons have been shown to swell across a variety of different conditions, including increases in extracellular potassium concentration (^[K+]o). The mechanisms involved in the coupling of K+ influx to water movement into cells leading to cell swelling are not well understood and remain controversial. Here, we set out to determine the effects of ^[K+]o on rapid volume responses of hippocampal

When we think about the history of glial cells, Santiago Ramón y Cajal comes to mind, who in addition to receiving the Nobel Prize in 1906 for staining individual neurons, is also credited with being the first to be able to specifically stain astroglia (Cajal, 1913a). However, Cajal (1913b) was initially unable to stain a third set of small cells present in tissue sections which apparently did not

Iron is a key nutrient for normal central nervous system (CNS) development and function; thus, iron deficiency as well as iron excess may result in harmful effects in the CNS. Oligodendrocytes and astrocytes are crucial players in brain iron equilibrium. However, the mechanisms of iron uptake, storage, and efflux in oligodendrocytes and astrocytes during CNS development or under pathological situations

The purpose of this study was to research possible developmental alterations of the substantia nigra (SN) in sudden infant death syndrome (SIDS), a syndrome frequently attributed to arousal failure from sleep. Brain stems of 46 victims of sudden infant death, aged from 1 to about 7 months (4 to 30 postnatal weeks), were investigated. Twenty-six of these cases were diagnosed as SIDS, due to the lack

In ischemic stroke, vasopressin hypersecretion is a critical factor of cerebral swelling and brain injury. To clarify neural mechanisms underlying ischemic stroke-evoked vasopressin hypersecretion, we observed the effect of unilateral permanent middle cerebral artery occlusion (MCAO) in rats on astrocytic plasticity and vasopressin neuronal activity in the supraoptic nucleus (SON) as well as their

Acetylcholine (ACh) has been suggested to facilitate plasticity and improve functional recovery after different types of brain lesions. Interestingly, numerous studies have shown that striatal cholinergic interneurons are relatively resistant to acute ischemic insults, but whether ACh released by these neurons enhances functional recovery after stroke is unknown. We investigated the role of endogenous

Oxytocin, a hypothalamic neuropeptide essential for breastfeeding, is mainly produced in oxytocin neurons in the supraoptic nucleus (SON) and paraventricular nucleus. However, mechanisms underlying oxytocin secretion, specifically the involvement of hyperpolarization-activated cyclic nucleotide-gated channel 3 (HCN3) in oxytocin neuronal activity, remain unclear. Using a rat model of intermittent and

The levels of brain-derived neurotrophic factor (BDNF) in the corpus callosum have previously been shown to have a critical impact on oligodendrocyte (OLG) lineage cells during cuprizone-elicited demyelination. In particular, BDNF+/– mice exhibit greater losses in myelin protein levels compared to wild-type mice after cuprizone. To investigate whether OLGs may directly mediate these effects of BDNF

With confirmed coronavirus disease 2019 (COVID-19) cases surpassing the 18 million mark around the globe, there is an imperative need to gain comprehensive understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the main clinical manifestations of COVID-19 are associated with respiratory or intestinal symptoms, reports of neurological signs and symptoms are increasing

Fifty years have passed since the discovery of glial fibrillary acidic protein (GFAP) by Lawrence Eng and colleagues. Now recognized as a member of the intermediate filament family of proteins, it has become a subject for study in fields as diverse as structural biology, cell biology, gene expression, basic neuroscience, clinical genetics and gene therapy. This review covers each of these areas, presenting

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