Neuroscience
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Stress is an independent risk factor for cognitive impairment, with elevated plasma homocysteine (HCY) levels playing a crucial role in stress-induced cognitive decline. While the rise in plasma HCY levels is linked to abnormal peripheral catabolism, the impact of stress on HCY catabolism in the brain remains unclear. This study investigated the effect of stress on HCY metabolism in the brain by analyzing HCY and its metabolic enzymes in the hippocampus and prefrontal cortex. ⋯ Immunofluorescence double-labeling revealed the downregulation of HCY metabolic enzymes in neurons of stressed mice. The transcription factor KLF4 (Kruppel-likefactor4), known for its inhibitory role, increased after stress or glucocorticoid treatment and suppressed the expression of MS, CBS, and CSE, contributing to elevated HCY levels in the brain. These findings offer new insights into the impairment of HCY catabolism in the stressed brain, suggesting that the downregulation of HCY metabolic enzymes may underlie HCY accumulation and exacerbate stress-induced cognitive dysfunction.
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Neural stem cells and/or progenitor cells (NSCs/NPCs) in the subventricular and subgranular zones of the adult mammal forebrain generate new neurons and are involved in partial repair after injury. Recently, NSCs/NPCs were identified in the area postrema (AP) of the medulla oblongata of the hindbrain. In this study, we used the properties of fenestrate capillaries to observe specific neuronal elimination in the AP of adult mice and investigated subsequent neuronal regeneration by neurogenesis. ⋯ Within 7 days of MSG administration, the number of BrdU+ Sox2+ and BrdU+ Math1+ cells increased markedly, and at least the BrdU+ Math1+ cells similarly increased for the next following 7 days. A remarkable number of HuC/D+ neurons with BrdU+ nuclei were observed 35 days after MSG administration. This study reveals that neurogenesis occurs in the AP of adult mice, recovering and maintaining normal neuronal density after neuronal death.
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Stress is triggered by a threatening event that alters the regulation of emotion, behavior, and cognition. The effects of stress on memory in animal models are well-documented. Firstly, this study aimed to determine whether the repeated forced swim stress (FSS) protocol induces memory impairment comparable to single prolonged stress (SPS) in the Y-maze test. ⋯ Mice underwent a Y-maze test, after which they were euthanized, and hippocampal samples were collected. (p-ClPhSe)2 pretreatment protected against the reduction in time spent in the novel arm by mice subjected to FSS. Repeated FSS exposure increased hippocampal protein levels of NMDAR subunits 2A, 2B, and EAAT1 compared to controls. (p-ClPhSe)2 pretreatment prevented this increase. In conclusion, (p-ClPhSe)2 mitigated stress-induced memory impairment in FSS-exposed mice, normalizing hippocampal NMDAR 2A, 2B, and EAAT1 protein levels.
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Obesity and drugs of abuse share overlapping neural circuits and behaviors. Silent synapses are transient synapses that are important for remodeling brain circuits. They are prevalent during early development but largely disappear by adulthood. ⋯ Using a dietary-induced obesity paradigm, mice that chronically consumed high fat diet (HFD) exhibited increased silent synapses in both direct and indirect pathway medium spiny neurons in the dorsolateral striatum. Both the time of onset of increased silent synapses and their normalization upon discontinuation of HFD occurs on an extended time scale compared to drugs of abuse. These data demonstrate that chronic consumption of HFD, like drugs of abuse, can alter mechanisms of circuit plasticity likely facilitating neural reorganization analogous to drugs of abuse.
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While mounting evidence suggests that scalp acupuncture (SA) may be effective in alleviating neurological deficits in patients with acute ischemic stroke (IS), its effect on remote hippocampal damage in acute IS and the underlying mechanisms remain elusive. Thus, proteomics analysis was conducted to identify potential targets of SA therapy in acute IS. SA significantly reduced cerebral infarct volume and attenuated neuronal damage in the ischemic penumbra and hippocampus, as well as alleviated neurological deficits in rats with middle cerebral artery occlusion (MCAO). ⋯ Proteomic analysis suggested that this effect is related to the modulation of the acute inflammatory response. SA attenuated remote hippocampal damage after IS by inhibiting microglia activation and neuroinflammation. Lastly, Kng1, Brd9, and Magl were identified as potential targets that mediate the anti-inflammatory effects of SA.