CADASIL from Bench to Bedside: Disease Models and Novel Therapeutic Approaches
AbstractCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenic disease caused byNOTCH3 mutations and characterized by typical clinical, neuroradiological, and pathological features. NOTCH3 belongs to a family of highly conserved transmembrane receptors rich of epidermal growth factor repeats, mostly expressed in vascular smooth muscle cells and pericytes, which perform essential developmental functions and are involved in tissues maintenance and renewal. To date, no therapeutic option for CADASIL is available except for few symptomatic treatments. Novel in vitro ...
Source: Molecular Neurobiology - January 19, 2021 Category: Neurology Source Type: research

Genomic Action of Sigma-1 Receptor Chaperone Relates to Neuropathic Pain
AbstractSigma-1 receptors (Sig-1Rs) are endoplasmic reticulum (ER) chaperones implicated in neuropathic pain. Here we examine if the Sig-1R may relate to neuropathic pain at the level of dorsal root ganglia (DRG). We focus on the neuronal excitability of DRG in a “spare nerve injury” (SNI) model of neuropathic pain in rats and find that Sig-1Rs likely contribute to the genesis of DRG neuronal excitability by decreasing the protein level of voltage-gated Cav2.2 as a translational inhibitor of mRNA. Specifically, during SNI, Sig-1Rs translocate from ER to the nuclear envelope via a trafficking protein Sec61β...
Source: Molecular Neurobiology - January 18, 2021 Category: Neurology Source Type: research

Modulators of Neuroinflammation Have a Beneficial Effect in a Lafora Disease Mouse Model
AbstractLafora disease (LD; OMIM#274780) is a fatal rare neurodegenerative disorder characterized by generalized epileptic seizures and the presence of polyglucosan inclusions (PGs), called Lafora bodies (LBs), typically in the brain. LD is caused by mutations in two genesEPM2A orEPM2B, which encode respectively laforin, a glucan phosphatase, and malin, an E3-ubiquitin ligase. Much remains unknown about the molecular bases of LD and, unfortunately, appropriate treatment is still missing; therefore patients die within 10  years from the onset of the disease. Recently, we have identified neuroinflammation as one of the ...
Source: Molecular Neurobiology - January 14, 2021 Category: Neurology Source Type: research

Cottonseed Oil Alleviates Ischemic Stroke-Induced Oxidative Stress Injury Via Activating the Nrf2 Signaling Pathway
In this study, we investigated the potential of CSO in regulating oxidative stress injury induced by middle cerebral artery occlusion and reperfusion (MCAO-R), or oxygen and glucose deprivation and reperfusion (OGD-R). We found that 1.3  mL/kg CSO treatment of male rats with a subcutaneous injection once every other day for 3 weeks significantly improved neurological deficit; reduced infarction volume; alleviated neuronal injuries; reduced the content of ROS and MDA; increased the activity of SOD, GSH, and GSH-PX; and markedly in creased the expression of Nrf2. Furthermore, treatment with 10−9 μL/mL...
Source: Molecular Neurobiology - January 14, 2021 Category: Neurology Source Type: research

Improvement of Rat Spinal Cord Injury Following Lentiviral Vector-Transduced Neural Stem/Progenitor Cells Derived from Human Epileptic Brain Tissue Transplantation with a Self-assembling Peptide Scaffold
AbstractSpinal cord injury (SCI) is a disabling neurological disorder that causes neural circuit dysfunction. Although various therapies have been applied to improve the neurological outcomes of SCI, little clinical progress has been achieved. Stem cell –based therapy aimed at restoring the lost cells and supporting micromilieu at the site of the injury has become a conceptually attractive option for tissue repair following SCI. Adult human neural stem/progenitor cells (hNS/PCs) were obtained from the epileptic human brain specimens. Induction of SCI was followed by the application of lentiviral vector-mediated green...
Source: Molecular Neurobiology - January 14, 2021 Category: Neurology Source Type: research

SARS-CoV-2 Infection in the Central and Peripheral Nervous System-Associated Morbidities and Their Potential Mechanism
AbstractThe recent outbreak of SARS-CoV-2 infections that causes coronavirus-induced disease of 2019 (COVID-19) is the defining and unprecedented global health crisis of our time in both the scale and magnitude. Although the respiratory tract is the primary target of SARS-CoV-2, accumulating evidence suggests that the virus may also invade both the central nervous system (CNS) and the peripheral nervous system (PNS) leading to numerous neurological issues including some serious complications such as seizures, encephalitis, and loss of consciousness. Here, we present a comprehensive review of the currently known role of SAR...
Source: Molecular Neurobiology - January 13, 2021 Category: Neurology Source Type: research

Myeloid TBK1 Deficiency Induces Motor Deficits and Axon Degeneration Through Inflammatory Cell Infiltration
ConclusionsBased on these data, inflammatory monocyte and macrophage infiltration and impaired innate immune defenses contribute to ALS and FTD. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - January 13, 2021 Category: Neurology Source Type: research

Ventral Tegmental Area Dysfunction and Disruption of Dopaminergic Homeostasis: Implications for Post-traumatic Stress Disorder
This article reviews recent advances in our knowledge of the relationship between dopaminergic dyshomeostasis and PTSD, including the contributions of specific dopaminergic gene variants to disease susceptibility, alterations in VTA dopamine neuron activity, dysregulation of dopaminergic transmission, and potential pharmacological and psychological interventions for PTSD targeting the dopaminergic system. An in-depth understanding of PTSD etiology is crucial for the development of innovative risk assessment, diagnostic, and treatment strategies following traumatic events. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - January 11, 2021 Category: Neurology Source Type: research

Fibroblast Growth Factor 9 Stimulates Neuronal Length Through NF-kB Signaling in Striatal Cell Huntington ’s Disease Models
AbstractProper development of neuronal cells is important for brain functions, and impairment of neuronal development may lead to neuronal disorders, implying that improvement in neuronal development may be a therapeutic direction for these diseases. Huntington ’s disease (HD) is a neurodegenerative disease characterized by impairment of neuronal structures, ultimately leading to neuronal death and dysfunctions of the central nervous system. Based on previous studies, fibroblast growth factor 9 (FGF9) may provide neuroprotective functions in HD, and FGFs may enhance neuronal development and neurite outgrowth. However...
Source: Molecular Neurobiology - January 9, 2021 Category: Neurology Source Type: research

LPS Preconditioning Attenuates Apoptosis Mechanism by Inhibiting NF- κB and Caspase-3 Activity: TLR4 Pre-activation in the Signaling Pathway of LPS-Induced Neuroprotection
AbstractNeuroinflammation, an inflammatory response within the nervous system, has been shown to be implicated in the progression of various neurodegenerative diseases. Recent in vivo studies showed that lipopolysaccharide (LPS) preconditioning provides neuroprotection by activating Toll-like receptor 4 (TLR4), one of the members for pattern recognition receptor (PRR) family that play critical role in host response to tissue injury, infection, and inflammation. Pre-exposure to low dose of LPS could confer a protective state against cellular apoptosis following subsequent stimulation with LPS at higher concentration, sugges...
Source: Molecular Neurobiology - January 9, 2021 Category: Neurology Source Type: research

NLRP3 Inflammasome Blockade Reduces Cocaine-Induced Microglial Activation and Neuroinflammation
We examined activation of the NLRP3 pathway in microglia exposed to cocaine, followed by validation in mice administered either cocaine or saline for 7 days, with or without pretreatment with the NLRP3 inhibitor, MCC950, and in postmortem cortical brain tissues of chronic cocaine-dependent humans. We found that microglia exposed to cocaine exhibited significant induction of NLRP3 and mature IL-1 β expression. Intriguingly, blockade of ROS (Tempol) attenuated cocaine-mediated priming of NLRP3 and microglial activation (CD11b). Blockade of NLRP3 by both pharmacological (MCC950) as well as gene silencing (siNLRP3) approa...
Source: Molecular Neurobiology - January 8, 2021 Category: Neurology Source Type: research

Pathophysiological Clues to How the Emergent SARS-CoV-2 Can Potentially Increase the Susceptibility to Neurodegeneration
AbstractAlong with emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019, a myriad of neurologic symptoms, associated with structural brain changes, were reported. In this paper, we provide evidence to critically discuss the claim that the survived patients could possibly be at increased risk for neurodegenerative diseases via various mechanisms. This virus can directly invade the brain through olfactory bulb, retrograde axonal transport from peripheral nerve endings, or via hematogenous or lymphatic routes. Infection of the neurons along with peripheral leukocytes activation resu...
Source: Molecular Neurobiology - January 8, 2021 Category: Neurology Source Type: research

Autophagy-Dependent Increased ADAM10 Mature Protein Induced by TFEB Overexpression Is Mediated Through PPAR α
AbstractNonamyloidogenic processing of amyloid precursor protein (APP) by augmenting ADAM10 is a promising therapeutic strategy for Alzheimer ’s disease (AD). Therefore identification of molecular pathways that regulate ADAM10 expression is crucial. Autophagy is strongly dysregulated in AD, and TFEB was recently shown to be a master regulator of autophagy-lysosome pathway (ALP). Here, we report that TFEB expression in HeLa cells increas ed ADAM10 mature form by 72% (p 
Source: Molecular Neurobiology - January 8, 2021 Category: Neurology Source Type: research

Effects of Chronic Photobiomodulation with Transcranial Near-Infrared Laser on Brain Metabolomics of Young and Aged Rats
AbstractSince laser photobiomodulation has been found to enhance brain energy metabolism and cognition, we conducted the first metabolomics study to systematically analyze the metabolites modified by brain photobiomodulation. Aging is often accompanied by cognitive decline and susceptibility to neurodegeneration, including deficits in brain energy metabolism and increased susceptibility of nerve cells to oxidative stress. Changes in oxidative stress and energetic homeostasis increase neuronal vulnerability, as observed in diseases related to brain aging. We evaluated and compared the cortical and hippocampal metabolic path...
Source: Molecular Neurobiology - January 8, 2021 Category: Neurology Source Type: research

Differential Age-Dependent Mitochondrial Dysfunction, Oxidative Stress, and Apoptosis Induced by Neonatal Hypoxia-Ischemia in the Immature Rat Brain
AbstractNeonatal hypoxia-ischemia (HI) is among the main causes of mortality and morbidity in newborns. Experimental studies show that the immature rat brain is less susceptible to HI injury, suggesting that changes that occur during the first days of life drastically alter its susceptibility. Among the main developmental changes observed is the mitochondrial function, namely, the tricarboxylic acid (TCA) cycle and respiratory complex (RC) activities. Therefore, in the present study, we investigated the influence of neonatal HI on mitochondrial functions, redox homeostasis, and cell damage at different postnatal ages in th...
Source: Molecular Neurobiology - January 8, 2021 Category: Neurology Source Type: research

Dual-Specificity Phosphatase 15 (DUSP15) Modulates Notch Signaling by Enhancing the Stability of Notch Protein
AbstractDual-specificity phosphatases (DUSPs) comprise a unique group of enzymes that dephosphorylate signaling proteins at both phospho-serine/threonine and phospho-tyrosine residues. Since Notch signaling is an essential pathway for neuronal cell fate determination and development that is also upregulated in Alzheimer ’s disease tissues, we sought to explore whether and how DUSPs may impact Notch processing. Our results show that overexpression of DUSP15 concomitantly and dose-dependently increased the steady-state levels of recombinant Notch (extracellular domain-truncated Notch, NotchΔE) protein and its cle...
Source: Molecular Neurobiology - January 8, 2021 Category: Neurology Source Type: research

Modified Snake α-Neurotoxin Averts β-Amyloid Binding to α7 Nicotinic Acetylcholine Receptor and Reverses Cognitive Deficits in Alzheimer’s Disease Mice
We report that mToxin reversibly inhibits α7AChR, though it attenuates Aβ-induced synaptic transmission abnormalities, and upregulates pathways supporting long-term potentiation and reducing apoptosis. Remarkably, mToxin demonstrates no toxicity in brain slices and mice. Moreover, its chronic intracerebroventricular administration improve s memory in AD-model animals. Our results point to unique mToxin neuroprotective properties, which might be tailored for the treatment of AD. Our methodology bridges the gaps in understanding Aβ-α7AChR interaction and represents a promising direction for further inve...
Source: Molecular Neurobiology - January 8, 2021 Category: Neurology Source Type: research

Phosphoenolpyruvate Carboxykinase (PCK) in the Brain Gluconeogenic Pathway Contributes to Oxidative and Lactic Injury After Stroke
AbstractTo demonstrate the role of the rate-limiting and ATP-dependent gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PCK) in oxidative and lactic stress and the effect of phenothiazine on PCK after stroke, a total of 168 adult male Sprague Dawley rats (3  months old, 280–300 g) underwent 2-h intraluminal middle cerebral artery occlusion (MCAO) and reperfusion for 6, 24, 48 h, or 7 days. Phenothiazine (chlorpromazine and promethazine (C+P)) (8 mg/kg) and 3-mercaptopicolinic acid (3-MPA, a PCK inhibitor, 100 μM) were administered at reperfusi on onset. The effects of phosphoen...
Source: Molecular Neurobiology - January 8, 2021 Category: Neurology Source Type: research

The Unfolded Protein Response in the Human Infant Brain and Dysregulation Seen in Sudden Infant Death Syndrome (SIDS)
This study indicates that subgroups of SIDS infants, defined by risk exposure, had activation of the UPR in several nuclei relating to p roprioception and motor control, suggesting that the UPR underlies the neuroreceptor system changes responsible for these physiological functions, leading to compromise in the pathogenesis of SIDS. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - January 8, 2021 Category: Neurology Source Type: research

Membrane Depolarization Inhibits BIM EL Upregulation but Prevents Neuronal Apoptosis Primarily by Increasing Cellular GSH Levels
AbstractSympathetic neurons deprived of nerve growth factor (NGF) die by apoptosis. Chronic depolarization with elevated concentrations of extracellular potassium ([K+]E) supports long-term survival of these and other types of neurons in culture. While depolarization has long been used to support neuronal cultures, little is known about the mechanism. We explored how chronic depolarization of NGF-deprived mouse sympathetic neurons in culture blocks apoptotic death. First, we determined the effects of elevated [K+]E on proapoptotic BH3-only proteins reported to be upregulated in sympathetic neurons after NGF withdrawal. Upr...
Source: Molecular Neurobiology - January 8, 2021 Category: Neurology Source Type: research

M üller Glia-Mediated Retinal Regeneration
AbstractM üller glia originate from neuroepithelium and are the principal glial cells in the retina. During retinal development, Müller glia are one of the last cell types to be born. In lower vertebrates, such as zebrafish, Müller glia possess a remarkable capacity for retinal regeneration following vario us forms of injury through a reprogramming process in which endogenous Müller glia proliferate and differentiate into all types of retinal cells. In mammals, Müller glia become reactive in response to damage to protect or to further impair retinal function. Although mammalian Müller glia hav...
Source: Molecular Neurobiology - January 8, 2021 Category: Neurology Source Type: research

Opioid System Contributes to the Trifluoromethyl-Substituted Diselenide Effectiveness in a Lifestyle-Induced Depression Mouse Model
In conclusion, the modulation of opioid and glucocorticoid receptors and the antioxidant property contributed to the (m-CF3-PhSe)2 antidepressant-like effect in young mice exposed to an energy-dense diet and ethanol intake. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - January 8, 2021 Category: Neurology Source Type: research

Aging-Dependent Mitophagy Dysfunction in Alzheimer ’s Disease
AbstractAlzheimer ’s disease (AD) is the most common late-onset dementia characterized by the deposition of extracellular amyloid plaques and formation of intracellular neurofibrillary tangles, which eventually lead to neuronal loss and cognitive deficits. Multiple lines of evidence indicate that mitochondrial dysf unction is involved in the initiation and progression of AD. As essential machinery for mitochondrial quality control, mitophagy plays a housekeeping role in neuronal cells by eliminating dysfunctional or excessive mitochondria. At present, mounting evidence support that the activity of mitophagy ma rkedly...
Source: Molecular Neurobiology - January 8, 2021 Category: Neurology Source Type: research

In vivo Validation of Bimolecular Fluorescence Complementation (BiFC) to Investigate Aggregate Formation in Amyotrophic Lateral Sclerosis (ALS)
AbstractAmyotrophic lateral sclerosis (ALS) is a form of motor neuron disease (MND) that is characterized by the progressive loss of motor neurons within the spinal cord, brainstem, and motor cortex. Although ALS clinically manifests as a heterogeneous disease, with varying disease onset and survival, a unifying feature is the presence of ubiquitinated cytoplasmic protein inclusion aggregates containing TDP-43. However, the precise mechanisms linking protein inclusions and aggregation to neuronal loss are currently poorly understood. Bimolecular fluorescence complementation (BiFC) takes advantage  of the association o...
Source: Molecular Neurobiology - January 7, 2021 Category: Neurology Source Type: research

Microglial Activation Modulates Neuroendocrine Secretion During Experimental Sepsis
In this study, we aimed to investigate the role of microglial activation in the neuroendocrine system functions during systemic inflammation. Wistar rats received an intracerebroventricular injection of the microglial activation inhibitor minocycline (100  μg/animal), shortly before sepsis induction by cecal ligation and puncture. At 6 and 24 h after surgery, hormonal parameters, central and peripheral inflammation, and markers of apoptosis and synaptic function in the hypothalamus were analyzed. The administration of minocycline decreased the pro duction of inflammatory mediators and the expression of cell de...
Source: Molecular Neurobiology - January 7, 2021 Category: Neurology Source Type: research

Directly Reprogrammed Neurons Express MAPT and APP Splice Variants Pertinent to Ageing and Neurodegeneration
In this study, we characterised the dynamics of theMAPT andAPP alternative splicing during a developmental time-course of porcine and murine cerebral cortices. We found age-dependent and species-specific isoform composition ofMAPT, including 3R and 4R isoforms in the porcine adult brain similar to that of the adult human brain. We converted adult and embryonic fibroblasts directly into induced neurons and found similar developmental patterns of isoform composition, notably, the 3R and 4R isoforms relevant to the pathogenesis of Alzheimer ’s disease. Also, we observed cell-type-specific isoform expression ofAPP transc...
Source: Molecular Neurobiology - January 7, 2021 Category: Neurology Source Type: research

Adenosine Signaling and Clathrin-Mediated Endocytosis of Glutamate AMPA Receptors in Delayed Hypoxic Injury in Rat Hippocampus: Role of Casein Kinase 2
AbstractChronic adenosine A1R stimulation in hypoxia leads to persistent hippocampal synaptic depression, while unopposed adenosine A2AR receptor stimulation during hypoxia/reperfusion triggers adenosine-induced post-hypoxia synaptic potentiation (APSP) and increased neuronal death. Still, the mechanisms responsible for this adenosine-mediated neuronal damage following hypoxia need to be fully elucidated. We tested the hypothesis that A1R and A2AR regulation by protein kinase casein kinase 2 (CK2) and clathrin-dependent endocytosis of AMPARs both contribute to APSPs and neuronal damage. The APSPs following a 20-min hypoxia...
Source: Molecular Neurobiology - January 7, 2021 Category: Neurology Source Type: research

Increasing Nrf2 Activity as a Treatment Approach in Neuropsychiatry
AbstractNuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor encoded byNFE2L2. Under oxidative stress, Nrf2 does not undergo its normal cytoplasmic degradation but instead travels to the nucleus, where it binds to a DNA promoter and initiates transcription of anti-oxidative genes. Nrf2 upregulation is associated with increased cellular levels of glutathione disulfide, glutathione peroxidase, glutathione transferases, thioredoxin and thioredoxin reductase. Given its key role in governing the cellular antioxidant response, upregulation of Nrf2 has been suggested as a common therapeutic target in neuro...
Source: Molecular Neurobiology - January 7, 2021 Category: Neurology Source Type: research

Inhibition of ASIC-Mediated Currents by Activation of Somatostatin 2 Receptors in Rat Dorsal Root Ganglion Neurons
AbstractSomatostatin (SST) and its analogues like octreotide (OCT) have analgesic effect on a variety of pain through peripheral SST receptors (SSTRs). However, the precise molecular mechanisms have not yet been fully elucidated. This research aimed to identify possible antinociceptive mechanisms, showing functional links of the SSTR2 and acid-sensing ion channels (ASICs). Herein, we reported that OCT inhibited the electrophysiological activity of ASICs in rat dorsal root ganglia (DRG) neurons. OCT concentration-dependently decreased the peak amplitude of acid-evoked inward currents, which were mediated by ASICs. OCT shift...
Source: Molecular Neurobiology - January 7, 2021 Category: Neurology Source Type: research

Functional Differences Between Two Kv1.1 RNA Editing Isoforms: a Comparative Study on Neuronal Overexpression in Mouse Prefrontal Cortex
AbstractThe Shaker-related potassium channel Kv1.1 subunit has important implications for controlling neuronal excitabilities. A particular recoding by A-to-I RNA editing at I400 of Kv1.1 mRNA is an underestimated mechanism for fine-tuning the properties of Kv1.1-containing channels. Knowledge about functional differences between edited (I400V) and non-edited Kv1.1 isoforms is insufficient, especially in neurons. To understand their different roles, the two Kv1.1 isoforms were overexpressed in the prefrontal cortex via local adeno-associated virus-mediated gene delivery. The I400V isoform showed a higher competitiveness in...
Source: Molecular Neurobiology - January 7, 2021 Category: Neurology Source Type: research

Lmo4 Deficiency Enhances Susceptibility to Cisplatin-Induced Cochlear Apoptosis and Hearing Loss
AbstractCisplatin, a potent chemotherapeutic drug, induces ototoxicity, which limits its clinical utility. Cisplatin-induced oxidative stress plays a causal role in cochlear apoptosis while the consequent nitrative stress leads to the nitration of LIM domain only 4 (LMO4), a transcriptional regulator, and decreases its cochlear expression levels. Here, we show a direct link between cochlear LMO4 and cisplatin-induced hearing loss by employing aLmo4 conditional knockout mouse model (Lmo4lox/lox; Gfi1Cre/+). Hair cell-specific deletion ofLmo4 did not alter cochlear morphology or affect hearing thresholds and otoacoustic emis...
Source: Molecular Neurobiology - January 7, 2021 Category: Neurology Source Type: research

Transcription Factor Motifs Associated with Anterior Insula Gene Expression Underlying Mood Disorder Phenotypes
AbstractMood disorders represent a major cause of morbidity and mortality worldwide but the brain-related molecular pathophysiology in mood disorders remains largely undefined. Because the anterior insula is reduced in volume in patients with mood disorders, RNA was extracted from the anterior insula postmortem anterior insula of  mood disorder samples and compared with unaffected controls for RNA-sequencing identification of differentially expressed genes (DEGs) in (a) bipolar disorder (BD;n = 37) versus (vs.) controls (n = 33), and (b) major depressive disorder (MDDn = 30) v...
Source: Molecular Neurobiology - January 7, 2021 Category: Neurology Source Type: research

Disrupted Excitatory Synaptic Contacts and Altered Neuronal Network Activity Underpins the Neurological Phenotype in PCDH19-Clustering Epilepsy (PCDH19-CE)
AbstractPCDH19-Clustering Epilepsy (PCDH19-CE) is an infantile onset disorder caused by mutation of the X-linkedPCDH19 gene. Intriguingly, heterozygous females are affected while hemizygous males are not. While there is compelling evidence that this disorder stems from the coexistence of WT and PCDH19-null cells, the cellular mechanism underpinning the neurological phenotype remains unclear. Here, we investigate the impact ofPcdh19 WT and KO neuron mosaicism on synaptogenesis and network activity. Using our previously established knock-in and knock-out mouse models, together with CRISPR-Cas9 genome editing technology, we d...
Source: Molecular Neurobiology - January 7, 2021 Category: Neurology Source Type: research

Neuroprotective Effects Against Cerebral Ischemic Injury Exerted by Dexmedetomidine via the HDAC5/NPAS4/MDM2/PSD-95 Axis
AbstractNumerous evidences have highlighted the efficient role of dexmedetomidine (DEX) in multi-organ protection. In the present study, the neuroprotective role of DEX on cerebral ischemic injury and the underlining signaling mechanisms were explored. In order to simulate cerebral ischemic injury, we performed middle cerebral artery occlusion in mice and oxygen-glucose deprivation in neurons. Immunohistochemistry, Western blot analysis, and RT-qPCR were used to examine expression of HDAC5, NPAS4, MDM2, and PSD-95 in hippocampus tissues of MCAO mice and OGD-treated neurons. MCAO mice received treatment with DEX and sh-PSD-...
Source: Molecular Neurobiology - January 7, 2021 Category: Neurology Source Type: research

Impaired Acquisition of Nicotine-Induced Conditioned Place Preference in Fatty Acid-Binding Protein 3 Null Mice
AbstractNicotine causes psychological dependence through its interactions with nicotinic acetylcholine receptors in the brain. We previously demonstrated that fatty acid-binding protein 3 (FABP3) colocalizes with dopamine D2 receptors (D2Rs) in the dorsal striatum, and FABP3 deficiency leads to impaired D2R function. Moreover, D2R null mice do not exhibit increased nicotine-induced conditioned place preference (CPP) following chronic nicotine administration. To investigate the role of FABP3 in nicotine-induced CPP, FABP3 knockout (FABP3−/−) mice were evaluated using a CPP apparatus following consecutive nicotin...
Source: Molecular Neurobiology - January 7, 2021 Category: Neurology Source Type: research

Neuroprotective Effects of Testosterone in Male Wobbler Mouse, a Model of Amyotrophic Lateral Sclerosis
This study analyzed the effects of testosterone in male symptomatic Wobblers. Controls or Wobblers received empty or testosterone-filled silastic tubes for 2 months. The cervical spinal cord from testosterone-treated Wobblers showed (1) similar androgen levels to untreated control and (2) increased levels of testosterone, and its 5α-reduced metabolites, 5α- dihydrotestosterone, and 3β-androstanediol, but (3) undetectable levels of estradiol compared to untreated Wobblers. Testosterone-treated controls showed comparable steroid concentrations to its untrea ted counterpart. In testosterone- treated Wobblers ...
Source: Molecular Neurobiology - January 7, 2021 Category: Neurology Source Type: research

Cholesterol Metabolism in Neurodegenerative Diseases: Molecular Mechanisms and Therapeutic Targets
AbstractCholesterol is an indispensable component of the cell membrane and plays vital roles in critical physiological processes. Brain cholesterol accounts for a large portion of total cholesterol in the human body, and its content must be tightly regulated to ensure normal brain function. Disorders of cholesterol metabolism in the brain are linked to neurodegenerative diseases, including Alzheimer ’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and other atypical cognitive deficits that arise at old age. However, the specific role of cholesterol metabolism disorder in the pathogene...
Source: Molecular Neurobiology - January 7, 2021 Category: Neurology Source Type: research

Resolvin D1 Attenuates Innate Immune Reactions in Experimental Subarachnoid Hemorrhage Rat Model
AbstractExcessive inflammation is a major cause contributing to early brain injury (EBI) and is associated with negative or catastrophic outcomes of subarachnoid hemorrhage (SAH). Resolvin D1 (RvD1) exerts strong anti-inflammatory and pro-resolving effects on either acute or chronic inflammation of various origin. Henceforth, we hypothesized that RvD1 potentially attenuates excessive inflammation in EBI following SAH. Therefore, we generated a filament perforation SAH model and administered 3 different doses (0.3, 0.6, and 1.2 nmol) of RvD1 after experimental SAH. Neurological scores, brain edema, and blood –brain ba...
Source: Molecular Neurobiology - January 7, 2021 Category: Neurology Source Type: research

Nuclear Receptor NR5A2 Promotes Neuronal Identity in the Adult Hippocampus
AbstractNeurogenesis in the dentate gyrus (DG) of the adult hippocampus is actively involved in brain homeostasis. Thus, identification of novel regulators in adult neurogenesis could significantly contribute to new therapies. We have recently unraveled the regulatory role of NR5A2 (also known as LRH1), a druggable orphan nuclear receptor, in embryonic neurogenesis. However, its involvement in adult neurogenesis is still an open question. Here we show that NR5A2 is differentially expressed in the DG of the adult hippocampus with neurons exhibiting higher levels of expression than adult neural stem/progenitor cells (aNSCs),...
Source: Molecular Neurobiology - January 7, 2021 Category: Neurology Source Type: research

Hippocampal and Prefrontal Cortical Brain Tissue Levels of Irisin and GDF15 Receptor Subunits in Children
We report that integrin-αV was detected at all ages in the prefront al cortex with levels greatest in adults. Integrin-αV was also detected in the hippocampus in all age groups. In contrast, integrin-β5 was detected in cortex and hippocampus largely restricted to infants. Co-expression of integrin-αV/β5 in the human infant hippocampus and cortex suggests the pos sibility that irisin has a more robust effect on the developing vs. the adult brain and may have implications for Zika virus infection in infants and young children. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - January 7, 2021 Category: Neurology Source Type: research

TSG101 Promotes the Proliferation, Migration, and Invasion of Human Glioma Cells by Regulating the AKT/GSK3 β/β-Catenin and RhoC/Cofilin Pathways
In conclusion, the above results suggest that the expression of TSG101 is elevated in glioma patients, which accelerates the proliferation, migration, and invasion of glioma cells by regulating the AKT/GSK3β/β-catenin and RhoC/Cofilin pathways. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - January 7, 2021 Category: Neurology Source Type: research

Alpha-Synuclein Antibody Characterization: Why Semantics Matters
AbstractIn protein aggregation disorders, we assume that, during the process of protein aggregation, different types of aggregated species (oligomers, protofibrils, fibrils, etc.) are formed, some of which can be toxic to cells/tissues/organs. Recent evidence from numerous studies in cell and animal models of disease suggest that oligomeric species of different proteins might be more toxic that the larger, fibrillar forms. However, we still lack definitive data on the nature of the toxic species, mostly due to our inability to detect and define the various protein species that form as protein aggregate. The terms used are ...
Source: Molecular Neurobiology - January 7, 2021 Category: Neurology Source Type: research

Brain Disease Network Analysis to Elucidate the Neurological Manifestations of COVID-19
AbstractAlthough COVID-19 largely causes respiratory complications, it can also lead to various extrapulmonary manifestations resulting in higher mortality and these comorbidities are posing a challenge to the health care system. Reports indicate that 30 –60% of patients with COVID-19 suffer from neurological symptoms. To understand the molecular basis of the neurologic comorbidity in COVID-19 patients, we have investigated the genetic association between COVID-19 and various brain disorders through a systems biology-based network approach and obs erved a remarkable resemblance. Our results showed 123 brain-related d...
Source: Molecular Neurobiology - January 6, 2021 Category: Neurology Source Type: research

Impact of COVID-19 in the Mental Health in Elderly: Psychological and Biological Updates
AbstractSince December 2019, the world has been experiencing the challenge of facing coronavirus disease-19 (COVID-19), a severe infectious disease caused by the new coronavirus, SARS-CoV-2. The individuals with the most severe symptoms and the highest risk of death are the elderly and those with chronic illness. Among chronic conditions, those with a certain degree of chronic inflammation may predispose to a more severe evolution of COVID-19. Elderly with psychiatric disorders can present a persistent inflammatory state, a characteristic of the age ’s immunological senescence, but the disorder can accentuate that. S...
Source: Molecular Neurobiology - January 6, 2021 Category: Neurology Source Type: research

AMPAr GluA1 Phosphorylation at Serine 845 in Limbic System Is Associated with Cardiac Autonomic Tone
This study investigated the association between HRV and neurochemistry biomarkers of synaptic plasticity in AMY and aHIP. HRV indices were obtained from the resting state electrocardiogram of patients with drug-resistant mesial temporal lobe epilepsy (MTLE,n = 18) and the levels of P-GluA1-Ser845 and P-GluA1-Ser831 in the AMY and aHIP resected during the epilepsy surgery. A backward stepwise multiple linear regression models were used to analyze the association between HRV and synaptic plasticity biomarkers controlling for imbalances in the distrib ution of sociodemographic, clinical, neuroimaging, and neuros...
Source: Molecular Neurobiology - January 6, 2021 Category: Neurology Source Type: research

Human HINT1 Mutant Proteins that Cause Axonal Motor Neuropathy Exhibit Anomalous Interactions with Partner Proteins
AbstractThe 14  kDa histidine triad nucleotide-binding protein 1 (HINT1) is critical to maintain the normal function of motor neurons. Thus, a series of human HINT1 mutants cause autosomal recessive axonal neuropathy with neuromyotonia. HINT1 establishes a series of regulatory interactions with signaling proteins , some of which are enriched in motor neurons, such as the type 1 sigma receptor or intracellular domain (ICD) of transmembrane teneurin 1, both of which are also implicated in motor disturbances. In a previous study, we reported the capacity of HINT1 to remove the small ubiquitin-like modifier (SUM O) from a...
Source: Molecular Neurobiology - January 6, 2021 Category: Neurology Source Type: research

Genetic Diversity of SARS-CoV2 and Environmental Settings: Possible Association with Neurological Disorders
AbstractThe new coronavirus (CoV), called novel coronavirus disease 2019 (COVID-19), belongs to the Coronaviridae family which was originated from the sea market in Wuhan city in China, at the end of the year 2019. COVID-19 and severe acute respiratory syndrome (SARS) are belonging to the same family (Coronaviridae). The current outbreak of COVID-19 creates public concern and threats all over the world and now it spreads out to more than 250 countries and territories. The researchers and scientists from all over  the world are trying to find out the therapeutic strategies to abate the morbidity and mortality rate ...
Source: Molecular Neurobiology - January 6, 2021 Category: Neurology Source Type: research

The Choroid Plexus Is an Alternative Source of Prolactin to the Rat Brain
AbstractAmong the more than 300 functions attributed to prolactin (PRL), this hormone has been associated with the induction of neurogenesis and differentiation of olfactory neurons especially during pregnancy, which are essential for maternal behavior. Despite the original hypothesis that PRL enters the central nervous system through a process mediated by PRL receptors (PRLR) at the choroid plexus (CP), recent data suggested that PRL transport into the brain is independent of its receptors. Based on transcriptomic data suggesting that PRL could be expressed in the CP, this work aimed to confirm PRL synthesis and secretion...
Source: Molecular Neurobiology - January 6, 2021 Category: Neurology Source Type: research

Telmisartan Inhibits the NLRP3 Inflammasome by Activating the PI3K Pathway in Neural Stem Cells Injured by Oxygen-Glucose Deprivation
AbstractAngiotensin II receptor blockers (ARBs) have been shown to exert neuroprotective effects by suppressing inflammatory and apoptotic responses. In the present study, the effects of the ARB telmisartan on the NLRP3 inflammasome induced by oxygen-glucose deprivation (OGD) in neural stem cells (NSCs) were investigated, as well as their possible association with the activation of the PI3K pathway. Cultured NSCs were treated with different concentrations of telmisartan and subjected to various durations of OGD. Cell counting, lactate dehydrogenase, bromodeoxyuridine, and colony-forming unit assays were performed to measur...
Source: Molecular Neurobiology - January 6, 2021 Category: Neurology Source Type: research

Exploring the Genetic Association of the ABAT Gene with Alzheimer ’s Disease
In this study, we performed an integrative study at the genetic and expression levels to investigate the potential genetic association between theABAT gene and AD. Through re-analyzing data from the currently largest meta-analysis of AD genome-wide association study (GWAS), we identified genetic variants in the 3 ’-UTR ofABAT as the top AD-associated SNPs (P 
Source: Molecular Neurobiology - January 6, 2021 Category: Neurology Source Type: research