MiR-124 and Small Molecules Synergistically Regulate the Generation of Neuronal Cells from Rat Cortical Reactive Astrocytes
In conclusion, we present a novel approach to inducing endogenous rat cortical reactive astrocytes into neurons through co-regulation involving miR-124 and three small molecules. Thus, our research has potential implications for inhibiting glial scar formation and promoting neuronal regeneration after central nervous system injury or disease. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - April 3, 2021 Category: Neurology Source Type: research

A New Approach to Model Sporadic Alzheimer ’s Disease by Intracerebroventricular Streptozotocin Injection in APP/PS1 Mice
AbstractAlzheimer ’s disease (AD) is the most common cause of dementia among elderly people. Majority of AD cases are sporadic (SAD) with unknown cause. Transgenic animal models closely reflect the familial (genetic) aspect of the disease but not the sporadic type. However, most new drug candidates which are tested positive in transgenic animal models failed in clinical studies so far. Herein, we aim to develop an AD animal model that combines most of the neuropathological features seen in sporadic AD in humans with amyloid plaques observed in transgenic mice. Four-month-old wild-type and APP/PS1 AD mice were given a...
Source: Molecular Neurobiology - April 2, 2021 Category: Neurology Source Type: research

Increased Response to 3,4-Methylenedioxymethamphetamine (MDMA) Reward and Altered Gene Expression in Zebrafish During Short- and Long-Term Nicotine Withdrawal
This study used zebrafish to explore gene expression changes associated with altered sensitivity to the rewarding effects of MDMA following 2-week exposure to nicotine and 2 –60 days of nicotine withdrawal. Reward responses to MDMA were assessed using a conditioned place preference (CPP) paradigm and gene expression was evaluated using quantitative real-time PCR of mRNA from whole brain samples from drug-treated and control adult zebrafish. Zebrafish pre-exposed for 2 weeks to nicotine showed increased conditioned place preference in response to low-dose, 0.1 mg/kg, MDMA compared to un-exposed fish at 2, 7, 30 and 60...
Source: Molecular Neurobiology - March 5, 2021 Category: Neurology Source Type: research

Long Non-coding RNAs as Promising Therapeutic Approach in Ischemic Stroke: a Comprehensive Review
AbstractIn recent years, ischemic stroke (IS) has been one of the major causes of disability and mortality worldwide. The general mechanism of IS is based on reduced blood supply to neuronal tissue, resulting in neuronal cell damage by various pathological reactions. One of the main techniques for acute IS treatment entails advanced surgical approaches for restoration of cerebral blood supply but this is often associated with secondary brain injury, also known as ischemic reperfusion injury (I/R injury). Many researches have come to emphasize the significant role of long non-coding RNAs (lncRNAs) in IS, especially in I/R i...
Source: Molecular Neurobiology - March 5, 2021 Category: Neurology Source Type: research

Pivotal Role of Fyn Kinase in Parkinson ’s Disease and Levodopa-Induced Dyskinesia: a Novel Therapeutic Target?
AbstractThe exact etiology of Parkinson ’s disease (PD) remains obscure, although many cellular mechanisms including α-synuclein aggregation, oxidative damage, excessive neuroinflammation, and dopaminergic neuronal apoptosis are implicated in its pathogenesis. There is still no disease-modifying treatment for PD and the gold standard t herapy, chronic use of levodopa is usually accompanied by severe side effects, mainly levodopa-induced dyskinesia (LID). Hence, the elucidation of the precise underlying molecular mechanisms is of paramount importance. Fyn is a tyrosine phospho-transferase of the Src family nonre...
Source: Molecular Neurobiology - March 5, 2021 Category: Neurology Source Type: research

Genetic Analysis of Prosaposin, the Lysosomal Storage Disorder Gene in Parkinson ’s Disease
AbstractRecent genetic studies clearly indicate that variants in several lysosomal genes act as risk factors for idiopathic Parkinson ’s disease (PD). Variants in the co-activator of glucocerebrosidase gene (GBA) and the four active saposins (Sap A-D) which are encoded by the prosaposin gene (PSAP) are of particular interest; however, their genetic roles in PD are unknown. Whole-exome sequencing and Sanger sequencing were used to assess the genetic etiology of 400 autosomal dominant inherited PD (ADPD) and 300 sporadic PD (SPD) patients. Variants from public databases, including Genome Aggregation Database-East Asian...
Source: Molecular Neurobiology - March 5, 2021 Category: Neurology Source Type: research

Modulation of Brain Pathology by Enhancer RNAs in Cerebral Ischemia
AbstractRecent studies have reported widespread stimulus-dependent transcription of mammalian enhancers into noncoding enhancer RNAs (eRNAs), some of which have central roles in the enhancer-mediated induction of target genes and modulation of phenotypic outcomes during development and disease. In cerebral ischemia, the expression and functions of eRNAs are virtually unknown. Here, we applied genome-wide H3K27ac ChIP-seq and genome-wide RNA-seq to identify enhancer elements and stroke-induced eRNAs, respectively, in the mouse cerebral cortex during transient focal ischemia. Following a 1-h middle cerebral artery occlusion ...
Source: Molecular Neurobiology - March 5, 2021 Category: Neurology Source Type: research

Reactive Fibroblasts in Response to Optic Nerve Crush Injury
AbstractTraumatic optic neuropathy leads to bidirectional degeneration of retinal ganglion cells and axons and results in optic nerve scaring, which inhibits the regeneration of damaged axons. Compared with its glial counterpart, the fibrotic response causing nerve scar tissue is poorly permissive to axonal regeneration. Using collagen1 α1-GFP reporter mice, we characterize the development of fibrotic scar formation following optic nerve crush injury. We observe that perivascular collagen1α1 cells constitute a major cellular component of the fibrotic scar. We demonstrate that extracellular molecules and monocyt...
Source: Molecular Neurobiology - March 5, 2021 Category: Neurology Source Type: research

AMPA Receptor Expression Requirement During Long-Term Memory Retrieval and Its Association with mTORC1 Signaling
AbstractRecently, it was reported that mechanistic/mammalian target of rapamycin complex 1 (mTORC1) activity during memory retrieval is required for normal expression of aversive and non-aversive long-term memories. Here we used inhibitory-avoidance task to evaluate the potential mechanisms by which mTORC1 signaling pathway participates in memory retrieval. First, we studied the role of GluA-subunit trafficking during memory recall and its relationship with mTORC1 pathway. We found that pretest intrahippocampal infusion of GluR23 ɣ, a peptide that selectively blocks GluA2-containing AMPA receptor (AMPAR) endocytosis, prev...
Source: Molecular Neurobiology - March 5, 2021 Category: Neurology Source Type: research

Alteration of miRNA Biogenesis Regulating Proteins in the Human Microglial Cell Line HMC-3 After Ischemic Stress
AbstractMicroRNAs (miRNA) are small noncoding sequences that control apoptosis, proliferation, and neuroinflammatory pathways in microglia cells. The expression of distinct miRNAs is altered after ischemia in the brain. Only minor information is available about the biogenesis and maturation of miRNAs after ischemia. We aimed at examining the impact of oxygen-glucose deprivation (OGD) and hydrogen peroxide (H2O2) –induced stress on the expression of miRNA regulating proteins such as DROSHA, DGCR8, XPO5, DICER, TARBP2, and AGO2 in the cultured human microglial cell line HMC-3 (human microglial cell line clone 3). OGD d...
Source: Molecular Neurobiology - March 5, 2021 Category: Neurology Source Type: research

Hippocampal Sector –Specific Metabolic Profiles Reflect Endogenous Strategy for Ischemia-Reperfusion Insult Resistance
AbstractThe gerbil is a well-known model for studying cerebral ischemia. The CA1 of the hippocampus is vulnerable to 5 min of ischemia, while the CA2 –4 and dentate gyrus (DG) are resistant to it. Short-lasting ischemia, a model of transient ischemic attacks in men, results in CA1 neuron death within 2–4 days of reperfusion. Untargeted metabolomics, using LC-QTOF-MS, was used to enrich the knowledge about intrinsic vulnerability and resistanc e of hippocampal regions and their early post-ischemic response (IR). In total, 30 significant metabolites were detected. In controls, taurine was significantly lower and ...
Source: Molecular Neurobiology - March 5, 2021 Category: Neurology Source Type: research

Parkinson ’s Disease Master Regulators on Substantia Nigra and Frontal Cortex and Their Use for Drug Repositioning
AbstractParkinson ’s disease (PD) is among the most prevalent neurodegenerative diseases. Available evidences support the view of PD as a complex disease, being the outcome of interactions between genetic and environmental factors. In face of diagnosis and therapy challenges, and the elusive PD etiology, the use of alternative methodological approaches for the elucidation of the disease pathophysiological mechanisms and proposal of novel potential therapeutic interventions has become increasingly necessary. In the present study, we first reconstructed the transcriptional regulatory networks (TN), centered on transcri...
Source: Molecular Neurobiology - March 5, 2021 Category: Neurology Source Type: research

Rice Bran Extract Protected against LPS-Induced Neuroinflammation in Mice through Targeting PPAR- γ Nuclear Receptor
AbstractPPAR- γ anti-inflammatory functions have received significant attention since its agonists have been shown to exert a wide range of protective effects in many experimental models of neurologic diseases. Rice bran is very rich in polyunsaturated fatty acids, which are reported to act as PPAR-γ partial ag onists. Herein, the anti-inflammatory effect of rice bran extract (RBE) through PPAR-γ activation was evaluated in LPS-induced neuroinflammatory mouse model in comparison to pioglitazone (PG) using 80 Swiss albino mice. RBE (100 mg/kg) and PG (30 mg/kg) were given orally for 21 days ...
Source: Molecular Neurobiology - March 5, 2021 Category: Neurology Source Type: research

Dietary Protein Source Influences Brain Inflammation and Memory in a Male Senescence-Accelerated Mouse Model of Dementia
AbstractDementia is a pathological condition characterized by a decline in memory, as well as in other cognitive and social functions. The cellular and molecular mechanisms of brain damage in dementia are not completely understood; however, neuroinflammation is involved. Evidence suggests that chronic inflammation may impair cognitive performance and that dietary protein source may differentially influence this process. Dietary protein source has previously been shown to modify systemic inflammation in mouse models. Thus, we aimed to investigate the effect of chronic dietary protein source substitution in an ageing and dem...
Source: Molecular Neurobiology - March 5, 2021 Category: Neurology Source Type: research

Maternal Separation-Induced Histone Acetylation Correlates with BDNF-Programmed Synaptic Changes in an Animal Model of PTSD with Sex Differences
In this study, the extent of histone acetylation in the hippocampus (HIP) and the expression of BDNF were measured to determine whether BDNF influences risk of PTSD following MS in early life. Rat offspring were separated from their dams (3 h/day or 6 h/day from PND2~PND14). Then, pups were treated with a single prolonged stress (SPS) procedure when they reached adulthood (PND80). In animals stressed with the SPS procedure in adulthood, those that had increased MS intensity in childhood demonstrated more significant changes in performance on tests of anxiety, depression, and contextual fear memory. Reduced levels of total ...
Source: Molecular Neurobiology - March 5, 2021 Category: Neurology Source Type: research

Correction to: CORM-2-Solid Lipid Nanoparticles Maintain Integrity of Blood-Spinal Cord Barrier After Spinal Cord Injury in Rats
A Correction to this paper has been published:https://doi.org/10.1007/s12035-020-02233-5 (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - March 5, 2021 Category: Neurology Source Type: research

Retraction Note to: Effects of microRNA-21 on Nerve Cell Regeneration and Neural Function Recovery in Diabetes Mellitus Combined with Cerebral Infarction Rats by Targeting PDCD4
This article has been retracted. Please see the Retraction Notice for more detail:https://doi.org/10.1007/s12035-021-02334-9 (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - March 5, 2021 Category: Neurology Source Type: research

Intermittent Hypoxia Activates N -Methyl-D-Aspartate Receptors to Induce Anxiety Behaviors in a Mouse Model of Sleep-Associated Apnea
AbstractSleep apnea disrupts physiologic homeostasis and causes neuronal dysfunction. In addition to signs of mental disorders and cognitive dysfunction, patients with sleep apnea have a higher anxiety rate. Here, we examined the mechanisms underlying this critical health issue. We used a mouse model with sleep-associated chronic intermittent hypoxia (IH) to verify the effects of sleep apnea on neuronal dysfunction. To evaluate how IH alters neuronal function to yield anxiety-like behavior and cognitive dysfunction, we examined synaptic plasticity and neuronal inflammation in related brain areas, including the medial prefr...
Source: Molecular Neurobiology - March 4, 2021 Category: Neurology Source Type: research

Metabolic Changes in Brain Slices over Time: a Multiplatform Metabolomics Approach
In this study, we used a multiplatform (LC-MS and GC-MS) untargeted metabolomics-based approach to shed light on the metabolome and lipidome changes taking place at different time intervals during the brain slice preparation process. We have found significant modifications in the levels of 300 compounds, including several lipid classes and their derivatives, as well as metabolites involved in the GABAergic pathway and the TCA cycle. All these preparation-dependent changes in the brain biochemistry related to the time interval should be taken into consideration for future studies to facilitate non-biased interpretations of ...
Source: Molecular Neurobiology - March 2, 2021 Category: Neurology Source Type: research

Neonatal Serotonin Depletion Induces Hyperactivity and Anxiolytic-like Sex-Dependent Effects in Adult Rats
AbstractThe serotoninergic system plays an important role in the ontogeny of the mammalian central nervous system, and changes in serotonin production during development may lead to permanent changes in brain cytoarchitecture and function. The present study investigated the programming effects of neonatal serotonin depletion on behavior and molecular components of the serotoninergic system in adult male and female rats. Subcutaneous para-chlorophenylalanine (pCPA) administration (100  mg kg−1) was performed daily on postnatal days 8 –16 to deplete brain serotonin content. During adulthood, elevated pl...
Source: Molecular Neurobiology - February 11, 2021 Category: Neurology Source Type: research

Relationship Between Genetic Variants of ACAT1 and APOE with the Susceptibility to Dementia (SADEM Study)
This study evaluates the relationship betweenACAT1 andAPOE genetic variants with susceptibility for the development of Alzheimer ’s disease and other dementias. We examined fourACAT1 polymorphisms (rs2247071, rs2862616, rs3753526, rs1044925) and two in theAPOE gene (rs7412, rs429358) in a group of 204 controls and 196 cases of dementia. Our results show one protective haplotype: CGCA (OR  = 0.34, 95% CI = 0.23–0.46;p 
Source: Molecular Neurobiology - February 11, 2021 Category: Neurology Source Type: research

L-3-n-Butylphthalide improves synaptic and dendritic spine plasticity and ameliorates neurite pathology in Alzheimer ’s disease mouse model and cultured hippocampal neurons
In this study, we first of all confirmed the an ti-dementia effect of L-NBP in 13-month-old APP/PS1 mice, and then investigated the alterations in synaptic and dendritic spine plasticity due to L-NBP treatment both in vivo and in vitro. We also conducted preliminary studies and found the possible mechanisms related to the inhibition of over-activ ated complement cascade and the remodeling of actin cytoskeleton. Besides, we also found extra benefits of L-NBP on presynaptic dystrophic neurites and attempted to give explanations from the view of autophagy regulation. Taken together, our study added some new evidence to the ap...
Source: Molecular Neurobiology - February 11, 2021 Category: Neurology Source Type: research

Protective Role of Low Ethanol Administration Following Ischemic Stroke via Recovery of KCC2 and p75 NTR Expression
AbstractA striking result from epidemiological studies show a correlation between low alcohol intake and lower incidence for ischemic stroke and severity of derived brain injury. Although reduced apoptosis and inflammation has been suggested to be involved, little is known about the mechanism mediating this effect in vivo. Increase in intracellular chloride concentration and derived depolarizing GABAAR-mediated transmission are common consequences following various brain injuries and are caused by the abnormal expression levels of the chloride cotransporters NKCC1 and KCC2. Downstream pro-apoptotic signaling through p75NTR...
Source: Molecular Neurobiology - February 11, 2021 Category: Neurology Source Type: research

Stroke-Induced Peripheral Immune Dysfunction in Vitamin D –Deficient Conditions: Modulation by Progesterone and Vitamin D
AbstractVitamin D deficiency (Ddef) alters morphology and outcomes after a stroke. We investigated the interaction of Ddef following post-stroke systemic inflammation and evaluated whether administration of progesterone (P) or vitamin D (D) will improve outcomes. Ddef rats underwent stroke with lipopolysaccharide (LPS)-induced systemic inflammation. Rats were randomly divided into 9 groups and treated with P, D, or vehicle for 4 days. At day 4, rats were tested on different behavioral parameters. Markers of neuronal inflammation, endoplasmic reticulum stress, oxidative stress, white matter integrity, and apoptosis were mea...
Source: Molecular Neurobiology - February 11, 2021 Category: Neurology Source Type: research

Estrogen Attenuates Traumatic Brain Injury by Inhibiting the Activation of Microglia and Astrocyte-Mediated Neuroinflammatory Responses
In this study, we constructed an adult male mouse model of TBI and immediately after injury treated the mice with 17 β-estradiol (E2) (100 μg/kg, once every day via intraperitoneal injection) for 3 days. We found that E2 treatment significantly alleviated TBI-induced neurological deficits, neuronal injuries, and brain edema and significantly inhibited Iba1 and GFAP expression, which are markers of microglia an d astrocyte activation, respectively. E2 treatment also significantly inhibited TLR4 and NF-κB protein expression, and significantly reduced the expression of theproinflammatory factors IL-1 &...
Source: Molecular Neurobiology - February 11, 2021 Category: Neurology Source Type: research

Neuronal Protein Farnesylation Regulates Hippocampal Synaptic Plasticity and Cognitive Function
This study shows that in contrast to the detrimental effects of GGT reduction, systemic haplodeficiency of FT has little to no impact on hippocampal synaptic plasticity and cognition. However, forebrain neuron-specific FT deletion also leads to reduced synaptic plasticity, memory retention, and hippocampal dendritic spine density. Furthermore, a novel prenylomic analysis identifies distinct pools of prenylated proteins that are affected in the brain of forebrain neuron-specific FT and GGT knockout mice, respectively. Taken together, this study uncovers that physiological levels of FT and GGT in neurons are essential for no...
Source: Molecular Neurobiology - February 11, 2021 Category: Neurology Source Type: research

Hypothyroidism Induces Interleukin-1-Dependent Autophagy Mechanism as a Key Mediator of Hippocampal Neuronal Apoptosis and Cognitive Decline in Postnatal Rats
AbstractThyroid hormone (TH) is essential for brain development, and hypothyroidism induces cognitive deficits in children and young adults. However, the participating mechanisms remain less explored. Here, we examined the molecular mechanism, hypothesizing the involvement of a deregulated autophagy and apoptosis pathway in hippocampal neurons that regulate cognitive functions. Therefore, we used a rat model of developmental hypothyroidism, generated through methimazole treatment from gestation until young adulthood. We detected that methimazole stimulated the autophagy mechanism, characterized by increased LC3B-II, Beclin...
Source: Molecular Neurobiology - February 11, 2021 Category: Neurology Source Type: research

Chronic Escitalopram Treatment Does Not Alter the Effects of Neonatal Stress on Hippocampal BDNF Levels, 5-HT 1A Expression and Emotional Behaviour of Male and Female Adolescent Rats
AbstractEarly life stress is considered a risk factor for the development of long-term psychiatric disorders. Maternal deprivation (MD) is a useful paradigm to understand the neurobiological underpinnings of early stress-induced changes in neurodevelopment trajectory. The goal of the present study was to examine the effects of a chronic treatment with escitalopram (ESC) on the hippocampal levels of BDNF and neuropeptide Y (NPY), expression of serotonin type 1A receptor (5-HT1A), plasma corticosterone levels and emotional behaviours in male and female adolescent rats submitted to MD at 9  days of life (group DEP9) and ...
Source: Molecular Neurobiology - February 11, 2021 Category: Neurology Source Type: research

Intranasal Insulin Enhances Intracerebroventricular Streptozotocin –Induced Decrease in Olfactory Discriminative Learning via Upregulation of Subventricular Zone–Olfactory Bulb Neurogenesis in the Rat Model
AbstractOlfactory perception and learning play a vital role in the animal ’s entire life for habituation and survival. Insulin and insulin receptor signaling is well known to modulate the olfactory function and is also involved in the regulation of neurogenesis. A very high density of insulin receptors is present in the olfactory bulb (OB), the brain area involved in th e olfactory function, where active adult neurogenesis also takes place. Hence, our study was aimed to explore the effect of intranasal insulin treatment and the involvement of the subventricular zone–olfactory bulb (SVZ-OB) neurogenesis on olfac...
Source: Molecular Neurobiology - February 11, 2021 Category: Neurology Source Type: research

Epigenetic Blockade of Hippocampal SOD2 Via DNMT3b-Mediated DNA Methylation: Implications in Mild Traumatic Brain Injury-Induced Persistent Oxidative Damage
In conclusion, DNMT3b-mediated DNA methylation plays a critical role in SOD2 gene regulation in the hippocampus, and the perturbations therein post rMTBI are detrimental to redox homeostasis manifesting into neurological consequences. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - February 11, 2021 Category: Neurology Source Type: research

Neuroprotective Effect of Fractalkine on Radiation-induced Brain Injury Through Promoting the M2 Polarization of Microglia
In conclusion, the FKN could a ttenuate RIBI through the microglia polarization toward M2 phenotype by binding to CX3CR1 on microglia. Our study unveiled an important role of FKN/CX3CR1 in RIBI, indicating that promotion of FKN/CX3CR1 axis could be a promising strategy for the treatment of RIBI. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - February 11, 2021 Category: Neurology Source Type: research

Leptin Contributes to Neuropathic Pain via Extrasynaptic NMDAR-nNOS Activation
AbstractLeptin is an adipocytokine that is primarily secreted by white adipose tissue, and it contributes to the pathogenesis of neuropathic pain in collaboration with N-methyl-D-aspartate receptors (NMDARs). Functional NMDARs are a heteromeric complex that primarily comprise two NR1 subunits and two NR2 subunits. NR2A is preferentially located at synaptic sites, and NR2B is enriched at extrasynaptic sites. The roles of synaptic and extrasynaptic NMDARs in the contribution of leptin to neuropathic pain are not clear. The present study examined whether the important role of leptin in neuropathic pain was related to synaptic...
Source: Molecular Neurobiology - February 11, 2021 Category: Neurology Source Type: research

Neonatal Sevoflurane Exposure Impairs Learning and Memory by the Hypermethylation of Hippocampal Synaptic Genes
In conclusion, neonatal exposure to sevoflurane can impair learning and memory through DNA methylation of synaptic genes. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - February 11, 2021 Category: Neurology Source Type: research

Role of Modulation of Hippocampal Glucose Following Pilocarpine-Induced Status Epilepticus
AbstractStatus epilepticus (SE) is defined as continuous and self-sustaining seizures, which trigger hippocampal neurodegeneration, mitochondrial dysfunction, oxidative stress, and energy failure. During SE, the neurons become overexcited, increasing energy consumption. Glucose uptake is increased via the sodium glucose cotransporter 1 (SGLT1) in the hippocampus under epileptic conditions. In addition, modulation of glucose can prevent neuronal damage caused by SE. Here, we evaluated the effect of increased glucose availability in behavior of limbic seizures, memory dysfunction, neurodegeneration process, neuronal activity...
Source: Molecular Neurobiology - February 11, 2021 Category: Neurology Source Type: research

Regulation of Prdx6 by Nrf2 Mediated Through aiPLA2 in White Matter Reperfusion Injury
AbstractHypoxia and reperfusion produces overproduction of ROS (reactive oxygen species), which may lead to mitochondrial dysfunction leading to cell death and apoptosis. Here, we explore the hypothesis that Prdx6 protects the spinal cord white matter from hypoxia-reperfusion injury and elucidate the possible mechanism by which Prdx6 elicits its protective effects. Briefly, rats were deeply anesthetized with isoflurane. A 30-mm section of the spinal cord was rapidly removed and placed in cold Ringer ’s solution (2–4 °C). The dissected dorsal column was exposed to hypoxia with 95% N2 and 5% CO2 and repe...
Source: Molecular Neurobiology - February 11, 2021 Category: Neurology Source Type: research

TRAK1-Mediated Abnormality of Mitochondrial Fission Increases Seizure Susceptibility in Temporal Lobe Epilepsy
AbstractMitochondrial dysfunction is closely related to the occurrence of epilepsy. Homeostasis of mitochondrial fusion and division can alleviate mitochondrial dysfunction. The trafficking kinesin protein 1 (TRAK1) is a key regulator of mitochondrial movement and regulates mitochondrial fusion-fission balance. The pathogenic variants in TRAK1 result in the severe neurodevelopmental disorders. However, the role of TRAK1 in epilepsy remains unclear. In the present study, we report that TRAK1 has a crucial function in regulation of epileptogenesis in temporal lobe epilepsy (TLE). TRAK1 expression is decreased in the patient ...
Source: Molecular Neurobiology - February 11, 2021 Category: Neurology Source Type: research

Trehalose Ameliorates Seizure Susceptibility in Lafora Disease Mouse Models by Suppressing Neuroinflammation and Endoplasmic Reticulum Stress
AbstractLafora disease (LD) is one of the progressive and fatal forms of a neurodegenerative disorder and is characterized by teenage-onset myoclonic seizures. Neuropathological changes in LD include the formation of abnormal glycogen as Lafora bodies, gliosis, and neuroinflammation. LD is caused by defects in the gene coding for phosphatase (laforin) or ubiquitin ligase (malin). Mouse models of LD, developed by targeted disruption of these two genes, develop most symptoms of LD and show increased susceptibility to induced seizures. Studies on mouse models also suggest that defective autophagy might contribute to LD etiolo...
Source: Molecular Neurobiology - February 11, 2021 Category: Neurology Source Type: research

Nuclear Envelope and Nuclear Pore Complexes in Neurodegenerative Diseases —New Perspectives for Therapeutic Interventions
AbstractTransport of proteins, transcription factors, and other signaling molecules between the nucleus and cytoplasm is necessary for signal transduction. The study of these transport phenomena is particularly challenging in neurons because of their highly polarized structure. The bidirectional exchange of molecular cargoes across the nuclear envelope (NE) occurs through nuclear pore complexes (NPCs), which are aqueous channels embedded in the nuclear envelope. The NE and NPCs regulate nuclear transport but are also emerging as relevant regulators of chromatin organization and gene expression. The alterations in nuclear t...
Source: Molecular Neurobiology - February 11, 2021 Category: Neurology Source Type: research

Glucocorticoid Receptor Activation Restores Learning Memory by Modulating Hippocampal Plasticity in a Mouse Model of Brain Vitamin B 12 Deficiency
AbstractCobalamin (Cbl, vitamin B12) deficiency or inborn errors of Cbl metabolism can produce neurologic disorders resistant to therapies, including cognitive dysfunction, mild mental retardation, memory impairment, and confusion. We usedCd320 KO mouse as a model for studying the pathological mechanisms of these disorders.Cd320 encodes the receptor (TCblR) needed for the cellular uptake of Cbl in the brain. TheCd320−/− mouse model presented an impaired learning memory that could be alleviated by a moderate stress, which produced also a greater increase of plasma corticosterone, compared to wild type animals. T...
Source: Molecular Neurobiology - February 11, 2021 Category: Neurology Source Type: research

The Coding and Small Non-coding Hippocampal Synaptic RNAome
In conclusion, our data provide a valuable resource and point to several important targets for further research. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - February 10, 2021 Category: Neurology Source Type: research

Dexpramipexole Enhances K + Currents and Inhibits Cell Excitability in the Rat Hippocampus In Vitro
In this study, we performed electrophysiological experiments in vitro aimed to better characterize the impact of DEX on voltage-dependent currents and synaptic transmission in the hippocampus. By means of patch-clamp recordings on isolated hippocampal neurons, we found that DEX increases outward K+ currents evoked by a voltage ramp protocol. This effect is prevented by the non-selective voltage-dependent K+ channel (Kv) blocker TEA and by the selective small-conductance Ca2+-activated K+ (SK) channel blocker apamin. In keeping with this, extracellular field recordings from rat hippocampal slices also demonstrated that the ...
Source: Molecular Neurobiology - February 10, 2021 Category: Neurology Source Type: research

The Expanding Regulatory Mechanisms and Cellular Functions of Long Non-coding RNAs (lncRNAs) in Neuroinflammation
AbstractLncRNAs have emerged as important regulatory molecules in biological processes. They serve as regulators of gene expression pathways through interactions with proteins, RNA, and DNA. LncRNA expression is altered in several diseases of the central nervous system (CNS), such as neurodegenerative disorders, stroke, trauma, and infection. More recently, it has become clear that lncRNAs contribute to regulating both pro-inflammatory and anti-inflammatory pathways in the CNS. In this review, we discuss the molecular pathways involved in the expression of lncRNAs, their role and mechanism of action during gene regulation,...
Source: Molecular Neurobiology - February 8, 2021 Category: Neurology Source Type: research

Serum Creatinine Protects Against Amyotrophic Lateral Sclerosis: a Mendelian Randomization Study
This study provides evidence that sCr protects against ALS in European population but not in East Asian population. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - February 8, 2021 Category: Neurology Source Type: research

Insights from Animal Models on the Pathophysiology of Hyperphenylalaninemia: Role of Mitochondrial Dysfunction, Oxidative Stress and Inflammation
AbstractPhenylketonuria (PKU) is an inborn error of metabolism caused by phenylalanine hydroxylase (PAH) deficiency and characterized by elevated plasma levels of phenylalanine (hyperphenylalaninemia-HPA). In severe cases, PKU patients present with neurological dysfunction and hepatic damage, but the underlying mechanisms are not fully elucidated. Other forms of HPA also characterized by neurological symptoms occur in rare instances due to defects in the metabolism of the PAH cofactor tetrahydrobiopterin. This review aims to gather the knowledge acquired on the phenylalanine-induced toxicity focusing on findings obtained f...
Source: Molecular Neurobiology - February 6, 2021 Category: Neurology Source Type: research

Leukocyte Telomere Length in Patients with Multiple Sclerosis and Its Association with Clinical Phenotypes
AbstractAging is a significant factor influencing the course of multiple sclerosis (MS). Accelerated telomere attrition is an indicator of premature biological aging and a potential contributor to various chronic diseases, including neurological disorders. However, there is currently a lack of studies focusing on telomere lengths in patients with MS. We measured the average leukocyte telomere length (LTL) in biobanked DNA samples of 40 relapsing-remitting MS patients (RRMS), 20 primary progressive MS patients (PPMS), and 60 healthy controls using a multiplex quantitative polymerase chain reaction method. Changes in LTL ove...
Source: Molecular Neurobiology - February 5, 2021 Category: Neurology Source Type: research

Could α-Klotho Unlock the Key Between Depression and Dementia in the Elderly: from Animal to Human Studies
Abstractα-Klotho is known for its aging-related functions and is associated with neurodegenerative diseases, accelerated aging, premature morbidity, and mortality. Recent literature suggests that α-Klotho is also involved in the regulation of mental functions, such as cognition and psychosis. While most o f studies of α-Klotho are focusing on its anti-aging functions and protective role in dementia, increasing evidence showed many shared symptoms between depression and dementia, while depression has been proposed as the preclinical stage of dementia such as Alzheimer’s disease (AD). To see whether a...
Source: Molecular Neurobiology - February 1, 2021 Category: Neurology Source Type: research

Correction to: Genomic Action of Sigma-1 Receptor Chaperone Relates to Neuropathic Pain
A correction to this paper has been published: 10.1007/s12035-021-02310-3 (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - February 1, 2021 Category: Neurology Source Type: research

L-Citrulline Level and Transporter Activity Are Altered in Experimental Models of Amyotrophic Lateral Sclerosis
AbstractAmyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease caused by the death of the neurons regulating the voluntary muscles which leads to the progressive paralysis. We investigated the difference of transport function of L-citrulline in ALS disease model (NSC-34/hSOD1G93A, MT) and a control model (NSC-34/hSOD1wt, WT). The [14C]L-citrulline uptake was significantly reduced in MT cells as compared with that of control. The Michaelis-Menten constant (Km) for MT cells was 0.67  ± 0.05 mM, whereas it was 1.48 ± 0.21 mM for control. On the other hand,...
Source: Molecular Neurobiology - January 28, 2021 Category: Neurology Source Type: research

In Vivo Gene Delivery of STC2 Promotes Axon Regeneration in Sciatic Nerves
AbstractNeurons are vulnerable to injury, and failure to activate self-protective systems after injury leads to neuronal death. However, sensory neurons in dorsal root ganglions (DRGs) mostly survive and regenerate their axons. To understand the mechanisms of the neuronal injury response, we analyzed the injury-responsive transcriptome and found thatStc2 is immediately upregulated after axotomy.Stc2 is required for axon regeneration in vivo and in vitro, indicating thatStc2 is a neuronal factor regulating axonal injury response. The application of the secreted stanniocalcin 2 to injured DRG neurons promotes regeneration.St...
Source: Molecular Neurobiology - January 28, 2021 Category: Neurology Source Type: research

Regulation of Anxiety and Depression by Mitochondrial Translocator Protein-Mediated Steroidogenesis: the Role of Neurons
AbstractPharmacological studies have implicated the translocator protein (TSPO) in the regulation of complex behaviors including anxiety and depression, effects thought to be mediated by increased synthesis of neuroactive steroid hormones. However, TSPO function in the brain remains to be corroboratedin vivo via genetic studies. To address this, we developed global TSPO knockout (TSPO-KO) and neuronal TSPO transgenic (TSPO-Tg) mouse models to investigate TSPO function in the regulation of anxiety- and depression-related behaviors using elevated plus maze and forced swim test paradigms. Neuroactive steroid hormones were mea...
Source: Molecular Neurobiology - January 28, 2021 Category: Neurology Source Type: research