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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Previous research has shown that visual impairment results in reduced audio, tactile and proprioceptive ability. One hypothesis is that these issues arise from inaccurate body representations. Few studies have investigated metric body representations in a visually impaired population. ⋯ Our results showed thatblind participants overestimated their hands and feetto a similar degree. Sighted controls overestimated their hands significantly more than their feet. Taken together, our results partially support our hypothesis and suggest that visual deprivation, even for short periods result in hand size overestimation.
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Several experimental cerebral palsy models have been created to investigate cellular and molecular mechanisms involved in this condition and develop new therapeutic strategies. The model that has come closest to a motor phenotype similar to cerebral palsy is the one that combines perinatal anoxia with hindlimb sensorimotor restriction, as it induces visible changes at the peripheral and central levels. This systematic review with meta-analysis presents the impact of the cerebral palsy model that associates perinatal anoxia with hindlimb sensorimotor restriction on the nervous, muscular and skeletal systems. ⋯ The results of the meta-analysis reported a significant reduction in the media area of the soleus muscle fibers, increased number of glia cells and glia/neuron index in the somatosensory cortex, increased microglial activation in the hippocampus, and no changes in the corpus callosum thickness or neuron cells. The combination of perinatal anoxia and sensorimotor restriction entails muscle deficits and excessive activation of glial cells in brain areas. These results contribute to a methodological refinement of cerebral palsy models and favor new studies proposed for methodological elucidation in animal experimentation.
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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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Cellular senescence is involved in the progression of neurodegenerative diseases. Motor neurons exhibit senescence-like alterations in ALS. BRD7, identified as a regulatory factor associated with cellular senescence, its function in ALS remains unclear. ⋯ Knockdown of BRD7 inhibited p53 mitochondrial translocation, leading to reduced apoptosis. Our results suggest that BRD7 plays an important role in the survival of ALS motor neurons. BRD7 knockdown can reduce cellular senescence and apoptosis by inhibiting p21 and p53 mitochondrial translocation.