Remote but not Distant: a Review on Experimental Models and Clinical Trials in Remote Ischemic Conditioning as Potential Therapy in Ischemic Stroke
AbstractStroke is one of the main causes of neurological disability worldwide and the second cause of death in people over 65  years old, resulting in great economic and social burden. Ischemic stroke accounts for 85% of total cases, and the approved therapies are based on re-establishment of blood flow, and do not directly target brain parenchyma. Thus, novel therapies are urgently needed. In this review, limb remote isc hemic conditioning (RIC) is revised and discussed as a potential therapy against ischemic stroke. The review targets both (i) fundamental research based on experimental models and (ii) clinical resea...
Source: Molecular Neurobiology - October 22, 2021 Category: Neurology Source Type: research

Correction to: Involvement of Midbrain Dopamine Neuron Activity in Negative Reinforcement Learning in Mice
(Source: Molecular Neurobiology)
Source: Molecular Neurobiology - October 21, 2021 Category: Neurology Source Type: research

Sex-Stratified Single-Cell RNA-Seq Analysis Identifies Sex-Specific and Cell Type-Specific Transcriptional Responses in Alzheimer ’s Disease Across Two Brain Regions
AbstractAlzheimer ’s disease (AD) is a pervasive neurodegenerative disorder that disproportionately affects women. Since neural anatomy and disease pathophysiology differ by sex, investigating sex-specific mechanisms in AD pathophysiology can inform new therapeutic approaches for both sexes. Previous bulk human bra in RNA sequencing studies have revealed sex differences in dysregulated molecular pathways related to energy production, neuronal function, and immune response; however, the sex differences in disease mechanisms are yet to be examined comprehensively on a single-cell level. We leveraged nearly 74,00 0 cell...
Source: Molecular Neurobiology - October 20, 2021 Category: Neurology Source Type: research

Regulation of Brain Primary Cilia Length by MCH Signaling: Evidence from Pharmacological, Genetic, Optogenetic, and Chemogenic Manipulations
AbstractThe melanin-concentrating hormone (MCH) system is involved in numerous functions, including energy homeostasis, food intake, sleep, stress, mood, aggression, reward, maternal behavior, social behavior, and cognition. In rodents, MCH acts on MCHR1, a G protein-coupled receptor, which is widely expressed in the brain and abundantly localized to neuronal primary cilia. Cilia act as cells ’ antennas and play crucial roles in cell signaling to detect and transduce external stimuli to regulate cell differentiation and migration. Cilia are highly dynamic in terms of their length and morphology; however, it is not kn...
Source: Molecular Neurobiology - October 19, 2021 Category: Neurology Source Type: research

Melatonin Pretreatment Protects Against Status epilepticus, Glutamate Transport, and Oxidative Stress Induced by Kainic Acid in Zebrafish
AbstractStatus epilepticus (SE) develops from abnormal electrical discharges, resulting in neuronal damage. Current treatments include antiepileptic drugs. However, the most common drugs used to treat seizures may sometimes be ineffective and have many side effects. Melatonin is an endogenous physiological hormone that is considered an alternative treatment for neurological disorders because of its free radical scavenging property. Thus, this study aimed to determine the effects of melatonin pretreatment on SE by inducing glutamatergic hyperstimulation in zebrafish. Seizures were induced in zebrafish using kainic acid (KA)...
Source: Molecular Neurobiology - October 19, 2021 Category: Neurology Source Type: research

Environmental Enrichment Rescues Oxidative Stress and Behavioral Impairments Induced by Maternal Care Deprivation: Sex- and Developmental-Dependent Differences
This study investigated the action that early stress, represented by maternal deprivation (MD), has on the behavior and oxidative stress of Wistar female and male rats. Also, it was evaluated whether changes induced by MD could be reversed by environmental enrichment (EE). Male and female rats were divided into a non-MD and MD group. The MD group was subdivided into 3 groups: (1) assessed on the 31st day after exposure to EE for 10  days, (2) assessed on the 41st day after exposure to EE for 20  days, and (3) assessed on the 61st day after exposure to EE for 40  days. Behavioral tests were performed (memory ...
Source: Molecular Neurobiology - October 19, 2021 Category: Neurology Source Type: research

The Possible Protective Role of Dark Chocolate Against Acrylamide Neurotoxicity in Weaning Rats Cerebellum
In conclusion, DC can be used as effective supplement to decrease the dietary ACR cerebellar neuronal risks. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - October 18, 2021 Category: Neurology Source Type: research

Gene Therapy Approach with an Emphasis on Growth Factors: Theoretical and Clinical Outcomes in Neurodegenerative Diseases
This article mainly focu ses on the delivering modes of genetic materials in the CNS, which includes viral and non-viral vectors and their application in gene therapy. Despite the many clinical trials conducted so far, data have shown disappointing outcomes. The efforts done to improve outcomes, efficacy, and safety in the identification of targets in various neurological disorders are also discussed here. Adapting gene therapy as a new therapeutic approach for treating neurological disorders seems to be promising, with early detection and delivery of therapy before the neuron is lost, helping a lot the development of new ...
Source: Molecular Neurobiology - October 15, 2021 Category: Neurology Source Type: research

Lactate and Pyruvate Activate Autophagy and Mitophagy that Protect Cells in Toxic Model of Parkinson ’s Disease
AbstractIntracellular quality control regulated by autophagy process is important for maintenance of cellular homeostasis. Deregulation of autophagy and more specifically mitophagy leads to accumulation of the misfolded proteins and damaged mitochondria that in turn leads to the cell loss. Alteration of autophagy and mitophagy has shown to be involved in the number of disorders including neurodegenerative diseases. Autophagy and mitophagy could be activated by short-time acidification of the cytosol; however, most of the compounds which can induce it are toxic. Here, we tested several organic compounds which are involved i...
Source: Molecular Neurobiology - October 13, 2021 Category: Neurology Source Type: research

Ferrostatin-1 Alleviates White Matter Injury Via Decreasing Ferroptosis Following Spinal Cord Injury
AbstractSpinal cord injury (SCI), a devastating neurological impairment, usually imposes a long-term psychological stress and high socioeconomic burden for the sufferers and their family. Recent researchers have paid arousing attention to white matter injury and the underlying mechanism following SCI. Ferroptosis has been revealed to be associated with diverse diseases including stroke, cancer, and kidney degeneration. Ferrostatin-1, a potent inhibitor of ferroptosis, has been illustrated to curb ferroptosis in neurons, subsequently improving functional recovery after traumatic brain injury (TBI) and SCI. However, the role...
Source: Molecular Neurobiology - October 12, 2021 Category: Neurology Source Type: research

Differential Effects of Experimental Retinal Detachment on S- and M/L-Cones in Rats
AbstractRetinal detachment is a vision-threatening condition, which occurs when the neurosensory retina is separated from its blood supply. The main purpose of this study was to examine the effect of experimental retinal detachment in rats on cone photoreceptors. Retinal detachment was induced in the eyes of rats via subretinal injection of sodium hyaluronate. Experimental detachment caused a rapid, sustained loss of short (S)- and medium/long (M/L)-wavelength cone opsins. Importantly, S-opsin+ cones were affected earlier than M/L-opsin+ cones and were affected to a greater extent than M/L-opsin+ cones throughout the durat...
Source: Molecular Neurobiology - October 11, 2021 Category: Neurology Source Type: research

Role of Neurons and Glia Cells in Wound Healing as a Novel Perspective Considering Platelet as a Conventional Player
AbstractWound healing is a complex physiological process in which the damaged or injured tissue is replaced or regenerated by new cells or existing cells respectively in their synthesized and secreted matrices. Several cells modulate the process of wound healing including macrophages, fibroblasts, and keratinocytes. Apart from these cells, platelet has been considered as a major cellular fragment to be involved in wound healing at several stages by secreting its granular contents including growth factors, thus resulting in coagulation, inflammation, and angiogenesis. A distant cell, which is gaining significant attention n...
Source: Molecular Neurobiology - October 11, 2021 Category: Neurology Source Type: research

Midazolam Exposure Impedes Oligodendrocyte Development via the Translocator Protein and Impairs Myelination in Larval Zebrafish
AbstractAnesthetics are commonly used in various medical procedures. Accumulating evidence suggests that early-life anesthetics exposure in infants and children affects brain development, causing psychiatric and neurological disorders. However, the underlying mechanisms are poorly understood. Using zebrafish larvae as a model, we found that the proliferation and migration of oligodendrocyte progenitor cells (OPCs) were severely impaired by the exposure of midazolam (MDZ), an anesthetic widely used in pediatric surgery and intensive care medicine, leading to a reduction of oligodendroglial lineage cell in the dorsal spinal ...
Source: Molecular Neurobiology - October 9, 2021 Category: Neurology Source Type: research

Joint-Tissue Integrative Analysis Identified Hundreds of Schizophrenia Risk Genes
AbstractGenome-wide association studies (GWAS) have identified a large number of schizophrenia risk variants, and most of them are mapped to noncoding regions. By leveraging multiple joint-tissue gene expression data and GWAS data, we herein performed a transcriptome-wide association study (TWAS) and Mendelian randomization (MR) analysis and identified 144 genes whose mRNA levels were related to genetic risk of schizophrenia. Most of these genes exhibited diametrically opposite trends of expression in prenatal and postnatal brain tissues, despite that their expression levels in dorsolateral prefrontal cortex (DLPFC) tissue...
Source: Molecular Neurobiology - October 9, 2021 Category: Neurology Source Type: research

Correction to: Exposure to Short Photoperiod Regime Restores Spatial Cognition in Ventral Subicular Lesioned Rats: Potential Role of Hippocampal Plasticity, Glucocorticoid Receptors, and Neurogenesis
(Source: Molecular Neurobiology)
Source: Molecular Neurobiology - October 9, 2021 Category: Neurology Source Type: research

Mesenchymal Stem Cell-derived Extracellular Vesicles Transmitting MicroRNA-34a-5p Suppress Tumorigenesis of Colorectal Cancer Through c-MYC/DNMT3a/PTEN Axis
AbstractMesenchymal stem cell –derived extracellular vesicles (MSC-EV) can transport microRNAs (miRNAs) into colorectal cancer (CRC) cells, thus to inhibit the malignant phenotype of cancer cells. Whether MSC-EV could deliver miR-34a-5p to suppress CRC development was surveyed through the research. miR-34a-5p, c-MYC, DNA methy ltransferase 3a (DNMT3a), and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression were measured in CRC tissues and cell lines. miR-34a-5p and c-MYC expression were altered by transfection in HCT-116 cells. MSC-EV were transfected with miR-34a-5p- and c-MYC-related oligonuc...
Source: Molecular Neurobiology - October 8, 2021 Category: Neurology Source Type: research

Function of Oncogene Mycn in Adult Neurogenesis and Oligodendrogenesis
AbstractHumanMYCN is an oncogene amplified in neuroblastoma and many other tumors. Both humanMYCN and mouseMycn genes are important in embryonic brain development, but their functions in adult healthy nerve system are completely unknown. Here, withMycn-eGFP mice and quantitative RT-PCR, we found thatMycn was expressed in specific brain regions of young adult mice, including subventricular zone (SVZ), subgranular zone (SGZ), olfactory bulb (OB), subcallosal zone (SCZ), and corpus callosum (CC). With immunohistochemistry (IHC), we found that manyMycn-expressing cells expressed neuroblast marker doublecortin (DCX) and prolife...
Source: Molecular Neurobiology - October 8, 2021 Category: Neurology Source Type: research

NME1 Protects Against Neurotoxin-, α-Synuclein- and LRRK2-Induced Neurite Degeneration in Cell Models of Parkinson’s Disease
AbstractParkinson ’s disease (PD) is a neurodegenerative disease characterised by the progressive degeneration of midbrain dopaminergic neurons, coupled with the intracellular accumulation of α-synuclein. Axonal degeneration is a central part of the pathology of PD. While the majority of PD cases are sporadic, som e are genetic; the G2019S mutation in leucine-rich repeat kinase 2 (LRRK2) is the most common genetic form. The application of neurotrophic factors to protect dopaminergic neurons is a proposed experimental therapy. One such neurotrophic factor is growth differentiation factor (GDF)5. GDF5 is a dopa m...
Source: Molecular Neurobiology - October 8, 2021 Category: Neurology Source Type: research

Molecular Profiles of Amyloid- β Proteoforms in Typical and Rapidly Progressive Alzheimer’s Disease
We present a signature of 33 distinct pathophysiological proteoforms, including the commonly targeted Aβ40, A β42, A β4-42, A β11-42, and provide insight into their synthesis and quantities. Furthermore, we have validated the presence of highly hydrophobic A β seeds in rpAD brains that seeded reactions at a slower pace in comparison to typical Alzheimer’s disease. In vitro and in vivo analyses also verified variations in the molecular pathways modulated by brain-derived Aβ. These variations in the presence, synthesis, folding, and interactions of Aβ among sAD and rpAD brains constit...
Source: Molecular Neurobiology - October 7, 2021 Category: Neurology Source Type: research

Mdivi-1 Modulates Macrophage/Microglial Polarization in Mice with EAE via the Inhibition of the TLR2/4-GSK3 β-NF-κB Inflammatory Signaling Axis
In conclusion, these results indicate that Mdivi-1 significantly alleviates inflammation in mice with EAE by promoting M2 polarization by inhibiting TLR2/4- and GSK3β-mediated NF-κB activation. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - October 7, 2021 Category: Neurology Source Type: research

Nitric Oxide Signaling Pathway in Ventral Tegmental Area is Involved in Regulation of 7,8-Dihydroxyflavone on Alcohol Consumption in Rats
In this study, we determined the role of nitric oxide (NO), a pleiotropic signaling molecule, in the VTA in the action of 7,8-DHF upon alcohol drinking behavior. Intermittent alcohol exposure led to the overexpression of NO in the VTA, especially 72  h after withdrawal from four weeks of ethanol exposure in IA2BC rats. A higher amount of alcohol intake was also found at the same time point, consistent with the overexpression of NO in the VTA. Microinjection of NG-Nitro-l-Arginine Methyl Ester, (NO synthase inhibitor) or 2-4-carboxyphenyl-4,4,5 ,5-tetramethylimidazoline-1-oxyl-3-oxide (NO scavenger) into the VTA inhibi...
Source: Molecular Neurobiology - October 7, 2021 Category: Neurology Source Type: research

Correction to: Methamphetamine Enhances HIV-Induced Aberrant Proliferation of Neural Progenitor Cells via the FOXO3-Mediated Mechanism
(Source: Molecular Neurobiology)
Source: Molecular Neurobiology - October 6, 2021 Category: Neurology Source Type: research

α-Synuclein Induces the GSK-3-Mediated Phosphorylation and Degradation of NURR1 and Loss of Dopaminergic Hallmarks
This study provides a detailed analysis of the regulation of NURR1 stability by phosphorylation in synucleinopathies such as Parkinson’s disease.Graphical abstract (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - October 5, 2021 Category: Neurology Source Type: research

Neuroprotective Role of Acidosis in Ischemia: Review of the Preclinical Evidence
AbstractEfforts to develop effective neuroprotective therapies for ischemic stroke have had little success to date. One promising approach to neuroprotection is ischemic postconditioning, which utilizes brief bouts of ischemia after acute ischemic stroke to elicit neuroprotection, although the mechanism is largely unknown. As the primary components of transient ischemia are local hypoxia and acidosis, and hypoxic postconditioning has had little success, it is possible that the acidosis component may be the primary driver. To address the evidence behind this, we performed a systematic review of preclinical studies focused o...
Source: Molecular Neurobiology - October 4, 2021 Category: Neurology Source Type: research

Mechanism of Cellular Formation and In Vivo Seeding Effects of Hexameric β-Amyloid Assemblies
We report the early presence of hexameric-like Aβ assemblies in both transgenic mice brains exhibiting human Aβ pathology and in the cerebrospinal fluid of AD pa tients, suggesting hexameric Aβ as a potential early AD biomarker. Finally, cell-derived hexameric Aβ was found to seed other human Aβ forms, resulting in the aggravation of amyloid deposition in vivo and neuronal toxicity in vitro. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - October 4, 2021 Category: Neurology Source Type: research

Training Intensity, Not Duration, May Be Key to Upregulating Presynaptic Proteins of Calcium Dynamics and Calcium-Dependent Exocytosis in Fast- and Slow-Twitch Skeletal Muscles, in Addition to Maintaining Performance After Detraining
AbstractNeuromuscular adaptations are essential for improving athletic performance. However, little is known about the effect of different endurance training protocols and their subsequent detraining on the gene expression of critical factors for neuromuscular synaptic transmission. Therefore, this study investigated the effects of endurance training (high-intensity interval training [HIIT], continuous [cEND], mixed interval [Mix], and all protocols combined [Comb]) and detraining on performance and gene expression (GE) of the alpha-1a, synaptotagmin II (Syt-II), synaptobrevin II (Vamp2), and acetylcholinesterase (AChE) in...
Source: Molecular Neurobiology - October 4, 2021 Category: Neurology Source Type: research

Sigma-1 Receptor Activation Suppresses Microglia M1 Polarization via Regulating Endoplasmic Reticulum –Mitochondria Contact and Mitochondrial Functions in Stress-Induced Hypertension Rats
AbstractExposure to stress plays a detrimental role in the pathogenesis of hypertension via neuroinflammation pathways. Microglial neuroinflammation in the rostral ventrolateral medulla (RVLM) exacerbates stress-induced hypertension (SIH) by increasing sympathetic hyperactivity. Mitochondria of microglia are the regulators of innate immune response. Sigma-1R ( σ-1R) localizes to the mitochondria-associated membranes (MAMs) and regulates endoplasmic reticulum (ER) and mitochondria communication, in part through its chaperone activity. The present study aims to investigate the protective role of σ-1R on microglia...
Source: Molecular Neurobiology - October 2, 2021 Category: Neurology Source Type: research

Spared Nerve Injury Causes Sexually Dimorphic Mechanical Allodynia and Differential Gene Expression in Spinal Cords and Dorsal Root Ganglia in Rats
AbstractNeuropathic pain is more prevalent in women. However, females are under-represented in animal experiments, and the mechanisms of sex differences remain inadequately understood. We used the spared nerve injury (SNI) model in rats to characterize sex differences in pain behaviour, unbiased RNA-Seq and proteomics to study the mechanisms. Male and female rats were subjected to SNI- and sham-surgery. Mechanical and cold allodynia were assessed. Ipsilateral lumbar dorsal root ganglia (DRG) and spinal cord (SC) segments were collected for RNA-seq analysis with DESeq2 on Day 7. Cerebrospinal fluid (CSF) samples for proteom...
Source: Molecular Neurobiology - October 1, 2021 Category: Neurology Source Type: research

NIR Laser Photobiomodulation Induces Neuroprotection in an In Vitro Model of Cerebral Hypoxia/Ischemia
In conclusion, NIR laser radiation attenuates OGD neurotoxicity in organotypic hippocampal slices through attenuation of inflammatory mechanisms. These findings shed ligh t on molecular definition of NIR neuroprotective mechanisms, thus underlining the potential benefit of this technique for the treatment of cerebral ischemia. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - October 1, 2021 Category: Neurology Source Type: research

Role of TREM2 in Alzheimer ’s Disease: A Long Road Ahead
AbstractAlzheimer ’s disease (AD) is a neurodegenerative disease characterized by an increasing deterioration of memory, which is concomitant with additional cognitive deficits. Neurofibrillary tangles and senile plaques are two pivotal proteins inside the brain that are considered essential to obstruct the normal cognitive function of the brain. Genetic variations inTREM2 gene disturb the neuroinflammatory action of microglia in reducing the progression of the disease.TREM2 is a transmembrane receptor present on the microglia, which has an important function in neuroinflammation. Genome-wide association studies iden...
Source: Molecular Neurobiology - October 1, 2021 Category: Neurology Source Type: research

Aquaporin-4 Removal from the Plasma Membrane of Human M üller Cells by AQP4-IgG from Patients with Neuromyelitis Optica Induces Changes in Cell Volume Homeostasis: the First Step of Retinal Injury?
AbstractAquaporin-4 (AQP4) is the target of the specific immunoglobulin G autoantibody (AQP4-IgG) produced in patients with neuromyelitis optica spectrum disorders (NMOSD). Previous studies demonstrated that AQP4-IgG binding to astrocytic AQP4 leads to cell-destructive lesions. However, the early physiopathological events in M üller cells in the retina are poorly understood. Here, we investigated the consequences of AQP4-IgG binding to AQP4 of Müller cells, previous to the inflammatory response, on two of AQP4’s key functions, cell volume regulation response (RVD) and cell proliferation, a process closely a...
Source: Molecular Neurobiology - October 1, 2021 Category: Neurology Source Type: research

Therapeutic Assay with the Non-toxic C-Terminal Fragment of Tetanus Toxin (TTC) in Transgenic Murine Models of Prion Disease
AbstractThe non-toxic C-terminal fragment of the tetanus toxin (TTC) has been described as a neuroprotective molecule since it binds to Trk receptors and activates Trk-dependent signaling, activating neuronal survival pathways and inhibiting apoptosis. Previous in vivo studies have demonstrated the ability of this molecule to increase mice survival, inhibit apoptosis and regulate autophagy in murine models of neurodegenerative diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy. Prion diseases are fatal neurodegenerative disorders in which the main pathogenic event is the conversion of the cellular p...
Source: Molecular Neurobiology - October 1, 2021 Category: Neurology Source Type: research

Brain Exosomes: Friend or Foe in Alzheimer ’s Disease?
AbstractAlzheimer ’s disease (AD) is the most common neurodegenerative disease. It is known to be a multifactorial disease and several causes are associated with its occurrence as well as progression. However, the accumulation of amyloid beta (Aβ) is widely considered its major pathogenic hallmark. Additionally, n eurofibrillary tangles (NFT), mitochondrial dysfunction, oxidative stress, and aging (cellular senescence) are considered as additional hits affecting the disease pathology. Several studies are now suggesting important role of inflammation in AD, which shifts our thought towards the brain’s resid...
Source: Molecular Neurobiology - September 30, 2021 Category: Neurology Source Type: research

LISTERIN E3 Ubiquitin Ligase and Ribosome-Associated Quality Control (RQC) Mechanism
Abstract According to cellular demands, ribosomes synthesize and maintain the desired pool of proteins inside the cell. However, sometimes due to defects in ribosomal machinery and faulty mRNAs, these nascent polypeptides are constantly under threat to become non-functional. In such conditions, cells acquire the help of ribosome-associated quality control mechanisms (RQC) to eliminate such aberrant nascent proteins. The primary regulator of RQC is RING domain containing LISTERIN E3 ubiquitin ligase, which is associated with ribosomes and alleviates non-stop proteins –associated stress in cells. Mouse RING finger pr...
Source: Molecular Neurobiology - September 29, 2021 Category: Neurology Source Type: research

Melatonin Reduces Neuroinflammation and Improves Axonal Hypomyelination by Modulating M1/M2 Microglia Polarization via JAK2-STAT3-Telomerase Pathway in Postnatal Rats Exposed to Lipopolysaccharide
This study investigated whether melatonin would mitigate inflammation and alleviate the axonal hypomyelination in the corpus callosum in septic postnatal rats. We further explored if this might be related to the modulation of microglial polarization from M1 phenotype to M2 through the JAK2/STAT3/telomerase pathway. We reported here that indeed melatonin not only can it reduce the neurobehavioral disturbances in LPS-injected rats, but it can also dampen microglia-mediated inflammation. Thus, in LPS  + melatonin group, the expression of proinflammatory mediators in M1 phenotype microglia was downregulated. As o...
Source: Molecular Neurobiology - September 28, 2021 Category: Neurology Source Type: research

Gliotoxicity and Glioprotection: the Dual Role of Glial Cells
AbstractGlial cells (astrocytes, oligodendrocytes and microglia) are critical for the central nervous system (CNS) in both physiological and pathological conditions. With this in mind, several studies have indicated that glial cells play key roles in the development and progression of CNS diseases. In this sense, gliotoxicity can be referred as the cellular, molecular, and neurochemical changes that can mediate toxic effects or ultimately lead to impairment of the ability of glial cells to protect neurons and/or other glial cells. On the other hand, glioprotection is associated with specific responses of glial cells, by wh...
Source: Molecular Neurobiology - September 28, 2021 Category: Neurology Source Type: research

Sex and Estrous Cycle Differences in Analgesia and Brain Oxycodone Levels
AbstractSex differences in opioid analgesia occur in rodents and humans, and could be due to differences in drug and metabolite levels. Thus, we investigated the sex and cycle differences in analgesia (nociception) from oxycodone in rats and related these to sex and cycle differences in brain and plasma oxycodone and metabolite levels. Since numerous opioids are CYP2D enzyme substrates and variation in CYP2D alters opioid drug levels and response, we also initiated studies to see if the sex and cycle differences observed might be due to differences in brain CYP2D activity. Across oxycodone doses, females in diestrus had hi...
Source: Molecular Neurobiology - September 28, 2021 Category: Neurology Source Type: research

PAF Receptor Inhibition Attenuates Neuronal Pyroptosis in Cerebral Ischemia/Reperfusion Injury
AbstractIschemic stroke is an inflammation-related disease, during which process activation of NLRP3 inflammasome and subsequent pyroptosis play crucial roles. Platelet-activating factor (PAF) is a potent phospholipid regulator of inflammation which exerts its effect via binding specific PAF receptor (PAFR). However, whether PAFR contributes to pyroptosis during ischemia/reperfusion (I/R) injury remains to be elucidated. To explore the underlying effect of PAFR on ischemic stroke from the perspective of pyroptosis, mice were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) injury and primary cultures of m...
Source: Molecular Neurobiology - September 25, 2021 Category: Neurology Source Type: research

AKAP150 and its Palmitoylation Contributed to Pain Hypersensitivity Via Facilitating Synaptic Incorporation of GluA1-Containing AMPA Receptor in Spinal Dorsal Horn
In this study, we found that intraplantar injection of complete Freund's adjuvant (CFA) significantly increased the synaptic expression of AKAP150 and caused a reorganization of AKAP150 signaling complex in spinal dorsal horn. Knockdown of AKAP150 or interruption of its interactions with kinases effectively suppressed the CFA-induced synaptic expression of GluA1 subunit of AMPARs. Our data also showed that an upregulation of AKAP150 palmitoylation was involved in the synaptic redistribution of AKAP150. Inhibition of AKAP150 palmitoylation by expression of palmitoylation-defective mutant AKAP150 (C36, 123S) effectively repr...
Source: Molecular Neurobiology - September 24, 2021 Category: Neurology Source Type: research

Human Bone Marrow Mesenchymal Stem Cell –Derived Exosomes Attenuate Blood–Spinal Cord Barrier Disruption via the TIMP2/MMP Pathway After Acute Spinal Cord Injury
AbstractAfter spinal cord injury (SCI), destruction of the blood –spinal cord barrier (BSCB) results in infiltration of blood cells, such as neutrophils and macrophages, leading to permanent neurological dysfunction. Previous studies have shown that human bone marrow mesenchymal stem cell (BMSC)–derived exosomes have a beneficial neuroprotective effect in SCI models. However, whether BMSC-Exos contribute to the integrity of the BSCB has not been clarified. The purpose of this study was to investigate the mechanism of BMSC-Exo-induced changes in the permeability of the BSCB after SCI. Here, we first used BMSC-Ex...
Source: Molecular Neurobiology - September 23, 2021 Category: Neurology Source Type: research

Deregulated Protein Kinases: Friend and Foe in Ischemic Stroke
AbstractIschemic stroke is the third leading cause of mortality worldwide, but its medical management is still limited to the use of thrombolytics as a lifesaving option. Multiple molecular deregulations of the protein kinase family occur during the period of ischemia/reperfusion. However, experimental studies have shown that alterations in the expression of essential protein kinases and their pharmacological modulation can modify the neuropathological milieu and hasten neurophysiological recovery. This review highlights the role of key protein kinase members and their implications in the evolution of stroke pathophysiolog...
Source: Molecular Neurobiology - September 22, 2021 Category: Neurology Source Type: research

Serum Neurofilament Light: a Potential Diagnostic and Prognostic Biomarker in Obstetric Posterior Reversible Encephalopathy Syndrome
AbstractObstetric posterior reversible encephalopathy syndrome (PRES), caused by preeclampsia (PE) or eclampsia, is a clinical imaging syndrome and a critical maternal complication, with vasogenic edema in white matter as a typical imaging characteristic. Serum neurofilament light (NFL) is a marker of neuroaxonal injury. Therefore, we performed this study to explore the diagnostic and prognostic role of NFL in obstetric PRES. We used stored serum samples and clinical data obtained from 2148 PE or eclampsia patients from the Guangzhou Medical Centre for Critical Pregnant Women from January 2015 to January 2020. The serum NF...
Source: Molecular Neurobiology - September 22, 2021 Category: Neurology Source Type: research

The Prevailing Role of Topoisomerase 2 Beta and its Associated Genes in Neurons
AbstractTopoisomerase 2 beta (TOP2 β) is an enzyme that alters the topological states of DNA by making a transient double-strand break during the transcription process. The direct interaction of TOP2β with DNA strand results in transcriptional regulation of certain genes and some studies have suggested that a particular set of gene s are regulated by TOP2β, which have a prominent role in various stages of neuron from development to degeneration. In this review, we discuss the role of TOP2β in various phases of the neuron’s life. Based on the existing reports, we have compiled the list of genes, wh...
Source: Molecular Neurobiology - September 21, 2021 Category: Neurology Source Type: research

Aging-Dependent Downregulation of SUV39H1 Histone Methyltransferase Increases Susceptibility to Stress-Induced Depressive Behavior
AbstractAging induces cellular and molecular changes including gene expression alteration in the brain, which might be associated with aging-induced decrease in stress coping ability. In the present study, we investigate how aging changes the ability to cope with stress and increases sensitivity to stress. Aged mice show decreased expression of SUV39H1 histone methyltransferase and increased expression of Mkp-1 in the hippocampus. The siRNA-mediated knockdown of SUV39H1 increases Mkp-1 expression and suppresses p-CREB and Bdnf expression in HT22 cells and in the hippocampus of mice. Chromatin immunoprecipitation assays ind...
Source: Molecular Neurobiology - September 18, 2021 Category: Neurology Source Type: research

Application of Metabolomics to the Discovery of Biomarkers for Ischemic Stroke in the Murine Model: a Comparison with the Clinical Results
AbstractIschemic stroke (IS) is a major cause of mortality and disability worldwide. However, the pathogenesis of IS remains unknown, and methods for early prediction and diagnosis of IS are lacking. Metabolomics can be applied to biomarker discovery and mechanism exploration of IS by exploring metabolic alterations. In this review, 62 IS metabolomics studies in the murine model published from January 2006 to December 2020 in the PubMed and Web of Science databases were systematically reviewed. Twenty metabolites (e.g., lysine, phenylalanine, methionine, tryptophan, leucine, lactate, serine, N-acetyl-aspartic acid, and glu...
Source: Molecular Neurobiology - September 17, 2021 Category: Neurology Source Type: research

G α13 Contributes to LPS-Induced Morphological Alterations and Affects Migration of Microglia
In conclusion, we propose Gα13 as a critical factor in the regulation of morphological and functi onal properties of microglia during activation, which might become a target of intervention for the control of microglia inflammation. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - September 16, 2021 Category: Neurology Source Type: research

Lead (Pb)-induced oxidative stress mediates sex-specific autistic-like behaviour in Drosophila melanogaster
AbstractAutism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder characterised by three main behavioural symptoms: abnormal social interaction, verbal and non-verbal communication impairments, and repetitive and restricted activities or interests. Even though the exact aetiology of ASD remains unknown, studies have shown a link between genetics and environmental pollutants. Heavy metal lead (Pb), the environmental pollutant, is associated with ASD. Pb may also exhibit sex-specific ASD behaviour, as has been demonstrated in the global human populations.Drosophila melanogaster as a model has been used...
Source: Molecular Neurobiology - September 15, 2021 Category: Neurology Source Type: research

Inverse Correlation Between Alzheimer ’s Disease and Cancer: Short Overview
AbstractThe negative association between Alzheimer ’s disease (AD) and cancer suggests that susceptibility to one disease may protect against the other. When biological mechanisms of AD and cancer and relationship between them are understood, the unsolved problem of both diseases which still touches the growing human population could be overcome. Actual information about biological mechanisms and common risk factors such as chronic inflammation, age-related metabolic deregulation, and family history is presented here. Common signaling pathways, e.g., p53, Wnt, role of Pin1, and microRNA, are discussed as well. Much a...
Source: Molecular Neurobiology - September 14, 2021 Category: Neurology Source Type: research

Mitochondrial Abnormalities and Synaptic Damage in Huntington ’s Disease: a Focus on Defective Mitophagy and Mitochondria-Targeted Therapeutics
This article also discusses recent developments of cell and mouse models, cellular changes, mitochondrial abnormalities , DNA damage, bioenergetics, oxidative stress, mitophagy, and therapeutics strategies in HD. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - September 14, 2021 Category: Neurology Source Type: research

Generation and Characterization of a Skeletal Muscle Cell-Based Model Carrying One Single Gne Allele: Implications in Actin Dynamics
AbstractUDP-N-Acetyl glucosamine-2 epimerase/N-acetyl mannosamine kinase (GNE) catalyzes key enzymatic reactions in the biosynthesis of sialic acid. Mutation in GNE gene causes GNE myopathy (GNEM) characterized by adult-onset muscle weakness and degeneration. However, recent studies propose alternate roles of GNE in other cellular processes beside sialic acid biosynthesis, particularly interaction of GNE with α-actinin 1 and 2. Lack of appropriate model system limits drug and treatment options for GNEM as GNE knockout was found to be embryonically lethal. In the present study, we have generated L6 rat skeletal muscle...
Source: Molecular Neurobiology - September 12, 2021 Category: Neurology Source Type: research