Rare DNAJC7 Variants May Play a Minor Role in Chinese Patients with ALS
Abstract DnaJ heat shock protein family member C7 gene (DNAJC7) has been identified as a genetic risk factor for amyotrophic lateral sclerosis (ALS). In our study, we aimed to screen for rare variants inDNAJC7 in a large cohort of Chinese ALS patients, and investigate the genotype –phenotype correlation ofDNAJC7 in ALS. Four (0.19%) variants ofDNAJC7 with minor allele frequency (MAF) < 0.1% among 2124 patients were identified, including 1 protein-truncating variant and 3 missense variants, all of which were predicted to be damaging. The patients carrying variants ofDNAJC7 in our cohort tented to have a limb on...
Source: Molecular Neurobiology - March 27, 2024 Category: Neurology Source Type: research
Interaction Between HCN and Slack Channels Regulates mPFC Pyramidal Cell Excitability in Working Memory Circuits
AbstractThe ability of monkeys and rats to carry out spatial working memory tasks has been shown to depend on the persistent firing of pyramidal cells in the prefrontal cortex (PFC), arising from recurrent excitatory connections on dendritic spines. These spines express hyperpolarization-activated cyclic nucleotide-gated (HCN) channels whose open state is increased by cAMP signaling, and which markedly alter PFC network connectivity and neuronal firing. In traditional neural circuits, activation of these non-selective cation channels leads to neuronal depolarization and increased firing rate. Paradoxically, cAMP activation...
Source: Molecular Neurobiology - March 27, 2024 Category: Neurology Source Type: research
A Comparative Investigation of Axon-Blood Vessel Growth Interaction in the Regenerating Sciatic and Optic Nerves in Adult Mice
AbstractThe vascular and the nervous systems share similarities in addition to their complex role in providing oxygen and nutrients to all cells. Both are highly branched networks that frequently grow close to one another during development. Vascular patterning and neural wiring share families of guidance cues and receptors. Most recently, this relationship has been investigated in terms of peripheral nervous system (PNS) regeneration, where nerves and blood vessels often run in parallel so endothelial cells guide the formation of the B üngner bands which support axonal regeneration. Here, we characterized the vascular re...
Source: Molecular Neurobiology - March 27, 2024 Category: Neurology Source Type: research
Interleukin-6 Inhibits Expression of miR-204-5p, a Regulator of Oligodendrocyte Differentiation: Involvement of miR-204-5p in the Prevention of Chemical-Induced Oligodendrocyte Impairment
In this study, through in situ hybridization in combination with immunohistochemistry, we showed that microRNA-204-5p in the corpus callosum was mainly expressed in OLs immunoreactive with adenomatous polyposis coli (APC), an OL marker. We also found miR-204-5p expression in mature OLs was suppressed by the addition of interleukin-6 (IL-6). Moreover, IL-6-induced inhibition of miR-204-5p expression was blocked by the addition of the inhibitors specific for p38 mitogen-activated protein kinase (p38MAPK) or phosphatidylinositol 3-kinase (PI3K) pathway. We further utilized a rat model by feeding cuprizone (CPZ)-containing die...
Source: Molecular Neurobiology - March 27, 2024 Category: Neurology Source Type: research
The Role of Astrocytic Mitochondria in the Pathogenesis of Brain Ischemia
AbstractThe morbidity rate of ischemic stroke is increasing annually with the growing aging population in China. Astrocytes are ubiquitous glial cells in the brain and play a crucial role in supporting neuronal function and metabolism. Increasing evidence shows that the impairment or loss of astrocytes contributes to neuronal dysfunction during cerebral ischemic injury. The mitochondrion is increasingly recognized as a key player in regulating astrocyte function. Changes in astrocytic mitochondrial function appear to be closely linked to the homeostasis imbalance defects in glutamate metabolism, Ca2+ regulation, fatty acid...
Source: Molecular Neurobiology - March 27, 2024 Category: Neurology Source Type: research
Neuroimmune Connectomes in the Gut and Their Implications in Parkinson ’s Disease
AbstractThe gastrointestinal tract is the largest immune organ and it receives dense innervation from intrinsic (enteric) and extrinsic (sympathetic, parasympathetic, and somatosensory) neurons. The immune and neural systems of the gut communicate with each other and their interactions shape gut defensive mechanisms and neural-controlled gut functions such as motility and secretion. Changes in neuroimmune interactions play central roles in the pathogenesis of diseases such as Parkinson ’s disease (PD), which is a multicentric disorder that is heterogeneous in its manifestation and pathogenesis. Non-motor and premotor sym...
Source: Molecular Neurobiology - March 27, 2024 Category: Neurology Source Type: research
Classic Famous Prescription Kai-Xin-San Ameliorates Alzheimer ’s Disease via the Wnt/β-Catenin Signaling Pathway
In this study, the AD model rats were established by combining intraperitoneal injection of D-galactose (150 mg/kg/day) and intracerebral injection of Aβ25-35 (10 μL) to investigate the meliorative effect of KXS on AD and explore its mechanism. After 1-month KXS treatment, Morris water maze test showed that different doses of KXS all improved the cognitive impairment of AD rats. The results of hematoxylin and eosin staining, Nissl staining, and Tunnel staini ng showed that the neuron injury in the hippocampal CA1 region of the AD rats was markedly improved after KXS treatment. Concurrently, KXS reversed the levels of bio...
Source: Molecular Neurobiology - March 27, 2024 Category: Neurology Source Type: research
Teriflunomide Promotes Blood –Brain Barrier Integrity by Upregulating Claudin-1 via the Wnt/β-catenin Signaling Pathway in Multiple Sclerosis
AbstractThe blood –brain barrier (BBB) and tight junction (TJ) proteins maintain the homeostasis of the central nervous system (CNS). The dysfunction of BBB allows peripheral T cells infiltration into CNS and contributes to the pathophysiology of multiple sclerosis (MS). Teriflunomide is an approved drug for the tr eatment of MS by suppressing lymphocytes proliferation. However, whether teriflunomide has a protective effect on BBB in MS is not understood. We found that teriflunomide restored the injured BBB in the EAE model. Furthermore, teriflunomide treatment over 6 months improved BBB permeability and redu ced periph...
Source: Molecular Neurobiology - March 27, 2024 Category: Neurology Source Type: research
Resveratrol Prevents Cell Swelling Through Inhibition of SUR1 Expression in Brain Micro Endothelial Cells Subjected to OGD/Recovery
AbstractThe SUR1-TRPM4-AQP4 complex is overexpressed in the initial phase of edema induced after cerebral ischemia, allowing the massive internalization of Na+ and water within the brain micro endothelial cells (BMEC) of the blood-brain barrier. The expression of the Abcc8 gene encoding SUR1 depends on transcriptional factors that are responsive to oxidative stress. Because reactive oxygen species (ROS) are generated during cerebral ischemia, we hypothesized that antioxidant compounds might be able to regulate the expression of SUR1. Therefore, the effect of resveratrol (RSV) on SUR1 expression was evaluated in the BMEC ce...
Source: Molecular Neurobiology - March 27, 2024 Category: Neurology Source Type: research
Transplantation of MiR-28-5p-Modified BMSCs Promotes Functional Recovery After Spinal Cord Injury
AbstractTraumatic spinal cord injury (TSCI) is a prevalent central nervous system condition that imposes a significant burden on both families and society, affecting more than 2 million people worldwide. Recently, there has been increasing interest in bone marrow mesenchymal stem cell (BMSC) transplantation as a promising treatment for spinal cord injury (SCI) due to their accessibility and low immunogenicity. However, the mere transplantation of BMSCs has limited capacity to directly participate in the repair of host spinal cord nerve function. MiR-28-5p, identified as a key differentially expressed miRNA in spinal cord i...
Source: Molecular Neurobiology - March 27, 2024 Category: Neurology Source Type: research
Sevoflurane Exposure Induces Neuronal Cell Ferroptosis Initiated by Increase of Intracellular Hydrogen Peroxide in the Developing Brain via ER Stress ATF3 Activation
AbstractNeuronal cell death is acknowledged as the primary pathological basis underlying developmental neurotoxicity in response to sevoflurane exposure, but the exact mechanism remains unclear. Ferroptosis is a form of programmed cell death characterized by iron-dependent lipid peroxidation that is driven by hydrogen peroxide (H2O2) and ferrous iron through the Fenton reaction and participates in the pathogenesis of multiple neurological diseases. As stress response factor, activating transcription factor 3 (ATF3) can be activated by the PERK/ATF4 pathway during endoplasmic reticulum (ER) stress, followed by increased int...
Source: Molecular Neurobiology - March 27, 2024 Category: Neurology Source Type: research
Personalized Protein-Protein Interaction Networks Towards Unraveling the Molecular Mechanisms of Alzheimer ’s Disease
In this study, we adopted a personalized approach and analyzed the transcriptome data from 403 patients individually by mapping the data on a human protein-protein interaction network. Patient-specific subnetw orks were discovered and analyzed in terms of the genes in the subnetworks, enriched functional terms, and known AD genes. We identified several affected pathways that could not be captured by the bulk comparison. We also showed that our personalized findings point to patterns of alterations consist ent with the recently suggested AD subtypes. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - March 27, 2024 Category: Neurology Source Type: research
Th17 Cells and IL-17A in Ischemic Stroke
AbstractThe neurological injury and repair mechanisms after ischemic stroke are complex. The inflammatory response is present throughout stroke onset and functional recovery, in which CD4 + T helper(Th) cells play a non-negligible role. Th17 cells, differentiated from CD4 + Th cells, are regulated by various extracellular signals, transcription factors, RNA, and post-translational modifications. Th17 cells specifically produce interleukin-17A(IL-17A), which has been reported to have pro-inflammatory effects in many studies. Recently, experimental researches showed that Th17 cells and IL-17A play an important role ...
Source: Molecular Neurobiology - March 27, 2024 Category: Neurology Source Type: research
Current Insights of Nanocarrier-Mediated Gene Therapeutics to Treat Potential Impairment of Amyloid Beta Protein and Tau Protein in Alzheimer ’s Disease
AbstractAlzheimer ’s disease (AD), is the major type of dementia and most progressive, irreversible widespread neurodegenerative disorder affecting the elderly worldwide. The prime hallmarks of Alzheimer’s disease (AD) are beta-amyloid plaques (Aβ) and neurofibrillary tangles (NFT). In spite of recent advances a nd developments in targeting the hallmarks of AD, symptomatic medications that promise neuroprotective activity against AD are currently unable to treat degenerating brain clinically or therapeutically and show little efficacy. The extensive progress of AD therapies over time has resulted in the adv ent of dis...
Source: Molecular Neurobiology - March 27, 2024 Category: Neurology Source Type: research
Vilazodone, a Selective Serotonin Reuptake Inhibitor with Diminished Impact on Methylphenidate-Induced Gene Regulation in the Striatum: Role of 5-HT1A Receptor
AbstractSelective serotonin reuptake inhibitors (SSRIs), including fluoxetine, are frequently combined with medical psychostimulants such as methylphenidate (Ritalin), for example, in the treatment of attention-deficit hyperactivity disorder/depression comorbidity. Co-exposure to these medications also occurs with misuse of methylphenidate as a recreational drug by patients on SSRIs. Methylphenidate, a dopamine reuptake blocker, produces moderate addiction-related gene regulation. Findings show that SSRIs such as fluoxetine given in conjunction with methylphenidate potentiate methylphenidate-induced gene regulation in the ...
Source: Molecular Neurobiology - March 27, 2024 Category: Neurology Source Type: research
