M2 Microglia-derived Exosomes Promote Spinal Cord Injury Recovery in Mice by Alleviating A1 Astrocyte Activation
In this study, we isolated M2-EXOs and intravenously introduced them into mice with SCI. Considering the reciprocal communication between microglia and astroglia in both healthy and injured central nervous systems (CNSs), we subsequently focused on the influence of M2-EXOs on astrocyte phenotype regulation. Our findings indicated that M2-EXOs promoted neuron survival and axon preservation, reduced the lesion area, inhibited A1 astrocyte activation, and improved motor function recovery in SCI mice. Moreover, they inhibited the nuclear translocation of p65 and the activation of the NF- κB signalling pathway in A1 astrocytes...
Source: Molecular Neurobiology - February 17, 2024 Category: Neurology Source Type: research

GABAergic and inflammatory changes in the frontal cortex following neonatal PCP plus isolation rearing, as a dual-hit neurodevelopmental model for schizophrenia
AbstractThe pathogenesis of schizophrenia begins in early neurodevelopment and leads to excitatory-inhibitory imbalance. It is therefore essential that preclinical models used to understand disease, select drug targets and evaluate novel therapeutics encompass similar neurochemical deficits. One approach to improved preclinical modelling incorporates dual-hit neurodevelopmental insults, like neonatal administration of phencyclidine (PCP, to disrupt development of glutamatergic circuitry) then post-weaning isolation (Iso, to mimic adolescent social stress). We recently showed that male Lister-hooded rats exposed to PCP-Iso ...
Source: Molecular Neurobiology - February 16, 2024 Category: Neurology Source Type: research

Autophagy in Multiple Sclerosis: Phagocytosis and Autophagy of Oligodendrocyte Precursor Cells
Abstract   Multiple sclerosis (MS) is a leading cause of chronic neurological dysfunction in young to middle-aged adults, affecting approximately 2.5 million people worldwide. It is characterized by inflammation, multifocal demyelination, axonal loss, and white and gray matter gliosis. Autophagy is a highly conserved protein degradation pathway. Polymorphisms in autophagy-related genes have been implicated in a variety of autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, psoriasis and MS. However, the significance of autophagy in MS remains to be elucidated. This paper aims to explore the...
Source: Molecular Neurobiology - February 16, 2024 Category: Neurology Source Type: research

The Effects of PICALM rs3851179 and Age on Brain Atrophy and Cognition Along the Alzheimer ’s Disease Continuum
AbstractRs3851179, a variant of PICALM gene, and age are the risk factors of Alzheimer ’s disease (AD). AD is divided into early-onset AD (EOAD,< 65 years) and late-onset AD (LOAD, ≥ 65 years) by age. The purpose was to investigate the impact of different genotypes of PICALM rs3851179 on brain atrophy and cognitive decline across the AD continuum in different age groups. Four hundred seven cognitive normal (CN) controls, 362 mild cognitive impairment (MCI) patients, and 94 A D patients were enrolled to assess the interaction between AD continuum, age status, and PICALM on gray matter volume (GMV), global cognition, ...
Source: Molecular Neurobiology - February 16, 2024 Category: Neurology Source Type: research

Astrocyte Activation in the ACC Contributes to Comorbid Anxiety in Chronic Inflammatory Pain and Involves in The Excitation-Inhibition Imbalance
AbstractNeurons within the anterior cingulate cortex (ACC) orchestrate the co-occurrence of chronic pain and anxiety. The ACC hyperactivity plays a crucial role in the emotional impact of neuropathic pain. Astrocyte-mediated neuroinflammatory is responsible for regulating the balance between excitation-inhibition (E/I) in the brain. However, there is limited understanding of the possible contributions of astrocytes in the ACC to comorbidity of anxiety and chronic inflammatory pain. This paper aims to investigate the possible contribution of astrocytes in the ACC to the comorbidity between anxiety and chronic inflammatory p...
Source: Molecular Neurobiology - February 16, 2024 Category: Neurology Source Type: research

Role of m6A RNA Methylation in Ischemic Stroke
AbstractIschemic stroke is a prominent contributor to global morbidity and mortality rates. The intricate and diverse mechanisms underlying ischemia –reperfusion injury remain poorly comprehended. RNA methylation, an emerging epigenetic modification, plays a crucial role in regulating numerous biological processes, including immunity, DNA damage response, tumorigenesis, metastasis, stem cell renewal, adipocyte differentiation, circadian rhythm s, cellular development and differentiation, and cell division. Among the various RNA modifications, N6-methyladenosine (m6A) modification stands as the most prevalent in mammalian...
Source: Molecular Neurobiology - February 16, 2024 Category: Neurology Source Type: research

Photobiomodulation Increases M2-Type Polarization of Macrophages by Inhibiting Versican Production After Spinal Cord Injury
This study tried to give an interpretation on the mechanism of inflammation inhibition for PBM in the perspective of matrix regulation. Our results might provide light on the inflammation regulation after SCI. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - February 16, 2024 Category: Neurology Source Type: research

Melatonin Modulates Cell Cycle Dynamics and Promotes Hippocampal Cell Proliferation After Ischemic Injury in Neonatal Rats
AbstractPromoting neural cell proliferation may represent an important strategy for enhancing brain repair after developmental brain injury. The present study aimed to assess the effects of melatonin on cell proliferation after an ischemic injury in the developing hippocampus, focusing on cell cycle dynamics. After in vivo neonatal hypoxia –ischemia (HI), hippocampal cell cycle dynamics were assessed by flow cytometry, together with histological evaluation of dentate gyrus cellularity and proliferation. Melatonin significantly increased the number of proliferating cells in the G2/M phase as well as the proliferating cell...
Source: Molecular Neurobiology - February 15, 2024 Category: Neurology Source Type: research

m6A-Induced lncRNA MEG3 Promotes Cerebral Ischemia-Reperfusion Injury Via Modulating Oxidative Stress and Mitochondrial Dysfunction by hnRNPA1/Sirt2 Axis
The objective of this study is to investigate the mechanism underlying MEG3-regulated cerebral ischemia/reperfusion (I/R) injury. MCAO/R mouse model and OGD/R-treated HT-22 cell model were established. The cerebral I/R injury was monitored by TTC staining, neurological scoring, H&E and TUNEL assay. The levels of MEG3, hnRNPA1, Sirt2 and other key molecules were detected by qRT-PCR and western blot. Mitochondrial dysfunction was assessed by transmission Electron Microscopy (TEM), JC-1 and MitoTracker staining. Oxidative stress was monitored using commercial kits. Bioinformatics analysis, RIP, RNA pull-down assays and RN...
Source: Molecular Neurobiology - February 15, 2024 Category: Neurology Source Type: research

Casting Light on the Janus-Faced HMG-CoA Reductase Degradation Protein 1: A Comprehensive Review of Its Dualistic Impact on Apoptosis in Various Diseases
AbstractNowadays, it is well recognized that apoptosis, as a highly regulated cellular process, plays a crucial role in various biological processes, such as cell differentiation. Dysregulation of apoptosis is strongly implicated in the pathophysiology of numerous disorders, making it essential to comprehend its underlying mechanisms. One key factor that has garnered significant attention in the regulation of apoptotic pathways is HMG-CoA reductase degradation protein 1, also known as HRD1. HRD1 is an E3 ubiquitin ligase located in the endoplasmic reticulum (ER) membrane. Its primary role involves maintaining the quality c...
Source: Molecular Neurobiology - February 14, 2024 Category: Neurology Source Type: research

Exosomes: A Cellular Communication Medium That Has Multiple Effects On Brain Diseases
AbstractExosomes, as membranous vesicles generated by multiple cell types and secreted to extracellular space, play a crucial role in a range of brain injury –related brain disorders by transporting diverse proteins, RNA, DNA fragments, and other functional substances. The nervous system’s pathogenic mechanisms are complicated, involving pathological processes like as inflammation, apoptosis, oxidative stress, and autophagy, all of which result in bl ood-brain barrier damage, cognitive impairment, and even loss of normal motor function. Exosomes have been linked to the incidence and progression of brain disorders in re...
Source: Molecular Neurobiology - February 14, 2024 Category: Neurology Source Type: research

β2-Adrenergic Regulation of the Neuromuscular Transmission and Its Lipid-Dependent Switch
Abstractβ2-Adrenoceptors (β2-ARs) are the most abundant subtype of adrenergic receptors in skeletal muscles. Their activation via a stabilization of postsynaptic architecture has beneficial effects in certain models of neuromuscular disorders. However, the ability of β2-ARs to regulate neuromuscular tran smission at the presynaptic level is poorly understood. Using electrophysiological recordings and fluorescent FM dyes, we found that β2-AR activation with fenoterol enhanced an involvement of synaptic vesicles in exocytosis and neurotransmitter release during intense activity at the neuromuscular j unctions of mouse di...
Source: Molecular Neurobiology - February 14, 2024 Category: Neurology Source Type: research

H3K4 Trimethylation Mediate Hyperhomocysteinemia Induced Neurodegeneration via Suppressing Histone Acetylation by ANP32A
AbstractHomocysteine (Hcy) is an independent and serious risk factor for dementia, including Alzheimer ’s disease (AD), but the precise mechanisms are still poorly understood. In the current study, we observed that the permissive histone mark trimethyl histone H3 lysine 4 (H3K4me3) and its methyltransferase KMT2B were significantly elevated in hyperhomocysteinemia (HHcy) rats, with impairment of sy naptic plasticity and cognitive function. Further research found that histone methylation inhibited synapse-associated protein expression, by suppressing histone acetylation. Inhibiting H3K4me3 by downregulating KMT2B could ef...
Source: Molecular Neurobiology - February 14, 2024 Category: Neurology Source Type: research

Microglial Neuroinflammation-Independent Reversal of Demyelination of Corpus Callosum by Arsenic in a Cuprizone-Induced Demyelinating Mouse Model
AbstractDemyelination is the loss of myelin in CNS, resulting in damaged myelin sheath. Oxidative stress and neuroinflammation play a key role in inducing demyelinating diseases like MS; hence, controlling oxidative stress and neuroinflammation is important. Cuprizone (CPZ), a copper chelator, generates oxidative stress and neuroinflammation, thereby inducing demyelination. Therefore, the CPZ-induced demyelinating mouse model (CPZ model) is widely used in research. The present study was intended to unravel a mechanism of inhibition of demyelination by arsenic in a CPZ model, which is otherwise known for its toxicity. We in...
Source: Molecular Neurobiology - February 14, 2024 Category: Neurology Source Type: research

Enriched Environment Contributes to the Recovery from Neurotoxin-Induced Parkinson ’s Disease Pathology
AbstractParkinson ’s disease (PD) is a neurological disorder that affects dopaminergic neurons. The lack of understanding of the underlying molecular mechanisms of PD pathology makes treating it a challenge. Several pieces of evidence support the protective role of enriched environment (EE) and exercise on dopamine rgic neurons. The specific aspect(s) of neuroprotection after exposure to EE have not been identified. Therefore, we have investigated the protective role of EE on dopamine dysregulation and subsequent downregulation of DJ1 protein using in vitro and in vivo models of PD. Our study for the first tim e demonstr...
Source: Molecular Neurobiology - February 13, 2024 Category: Neurology Source Type: research