Neuroscience
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Prophylactic effects of N-acethylcysteine on inflammation-induced depression-like behaviors in mice.
Depression, affecting individuals worldwide, is a prevalent mental disease, with an increasing incidence. Numerous studies have been conducted on depression, yet its pathogenesis remains elusive. Recent advancements in research indicate that disturbances in synaptic transmission, synaptic plasticity, and reduced neurotrophic factor expression significantly contribute to depression's pathogenesis. ⋯ Following treatment with NAC, the previously mentioned levels improved, indicating an enhancement in both synaptic transmission and synaptic plasticity. Our results suggest that NAC exerts a protective effect on mouse models of inflammatory depression, potentially through the enhancement of synaptic transmission and plasticity, as well as the restoration of neurotrophic factor expression. These findings offer vital animal experimental evidence supporting NAC's role in mitigating inflammatory depressive behaviors.
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The cerebellum is known to control the proper balance of isometric muscular contractions that maintain body posture. Current optogenetic manipulations of the cerebellar cortex output, however, have focused on ballistic body movements, examining movement initiation or perturbations. Here, by optogenetic stimulations of cerebellar Purkinje cells, which are the output of the cerebellar cortex, we evaluate body posture maintenance. ⋯ We identify a module in the medial part of the anterior vermis which, through multiple muscle tone regulation, is involved in postural anti-gravity maintenance of the body. Moreover, we report an antero-posterior and medio-lateral functional segregation over the vermal lobules IV/V/VI. Taken together our results open new avenues for better understanding of the modular functional organization of the cerebellar cortex and its role in postural anti-gravity maintenance.
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Entorhinal cortex (EC) LIII and LII glutamatergic neurons make monosynaptic connections onto distal apical dendrites of hippocampal CA1 and CA2 pyramidal neurons (PNs), respectively, through perforant path (PP) projections. We previously reported that a brief train of PP stimuli evokes strong supralinear temporal summation of excitatory postsynaptic potentials (EPSPs) in CA1 PNs that requires NMDAR activation, with relatively little summation in CA2 PNs in mice of either sex. Here we provide evidence from combined immunogold electron microscopy, cell-type specific genetic deletion and pharmacology that the NMDARs required for supralinear temporal summation of the CA1 PP EPSP are presynaptic, located in the PP terminals. Moreover, we found that the number of NMDARs in PP terminals innervating CA1 PNs is significantly greater than that found in PP terminals innervating CA2 PNs, providing a potential explanation for the difference in temporal summation in these two classes of hippocampal PNs.
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Multiple sclerosis (MS), a prevalent neurological disorder, predominantly affects young adults and is characterized by chronic autoimmune activity. The study explores the immune system dysregulation in MS, highlighting the crucial roles of immune and non-neuronal cells in the disease's progression. This review examines the dual role of cytokines, with some like IL-6, TNF-α, and interferon-gamma (IFN-γ) promoting inflammation and CNS tissue injury, and others such as IL-4, IL-10, IL-37, and TGF-β fostering remyelination and protecting against MS. ⋯ Additionally, the effectiveness of immunomodulatory drugs such as IFN-β and CD20-targeting monoclonal antibodies (e.g., rituximab) in modulating immune responses is reviewed, highlighting their potential to reduce relapse rates and delaying MS progression. These insights emphasize the importance of immune system dysfunction in MS development and progression, guiding the development of new therapeutic strategies. The study underscores recent advancements in understanding MS's molecular pathways, opening avenues for more targeted and effective treatments.
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Neurodegenerative diseases, characterized by abnormal deposition of misfolded proteins, often present with progressive loss of neurons. Chronic neuroinflammation is a striking hallmark of neurodegeneration. Microglia, as the primary immune cells in the brain, is the main type of cells that participate in the formation of inflammatory microenvironment. ⋯ There are various sources of free mtDNA in microglial cytoplasm, but mitochondrial oxidative stress accumulation plays the vital role. The upregulation of cGas/STING pathway in microglia contributes to the abnormal and persistent microglial activation, accompanied by excessive secretion of neurotoxic inflammatory mediators such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), which exacerbates the damage of neurons and promotes the development of neurodegeneration. Currently, novel therapeutic approaches need to be found to delay the progression of neurodegenerative disorders, and regulation of the cGas/STING signaling in microglia may be a potential target.