Neuroscience
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A myriad of chemical modifications of DNA and histones involved in the epigenetic regulation of neural gene expression have been documented and studied in detail since many years. However, more recently, modifications in RNA and their implications for neural gene functions have been progressively investigated. ⋯ Concomitantly, multiple lines of evidence have associated FTO with neuropsychiatric disorders. In this review, we discuss how FTO can exert its effect by acting not only on m6A but also on O, N6-dimethyladenosine (m6Am) in different types of RNA and potentially influence the development of some major neuropsychiatric diseases.
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Histone deacetylase inhibitors (HDACis) have displayed neuroprotective effects in animal models of retinal ischemia/reperfusion (I/R) injury. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a redox-sensitive transcription factor responds to oxidative damage. We investigated the role of Nrf2 in retinal I/R injury, and further explored the mechanisms underlying Nrf2-mediated neuroprotection exerted by HDACi. ⋯ However, this trend was not continued after silencing Nrf2. Chromatin immunoprecipitation assay demonstrated that Nrf2 at the Ho-1 promoter significantly increased transcriptional activity after oxidative stress induction. Nrf2, which is dispensable in HDACi-mediated neuroprotection, plays a major neuroprotective role in retinal I/R injury.
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Intermittent and excessive ethanol consumption over very short periods of time, known as binge drinking, is common in the adolescence, considered a vulnerable period to the effects of alcohol in terms of cognitive performance. One of the brain functions most drastically affected by ethanol in adolescent individuals seems to be spatial learning and memory dependent on the hippocampus. In the current study we have focused on the long-lasting effects on spatial learning and memory of intermittent and excessive alcohol consumption compared to chronic and moderate alcohol exposure during adolescence. ⋯ Hippocampal expression of AMPA and NMDA receptor subunits as well as levels of phosphorylated Ser9-GSK3β (the inactive form of GSK3β) were also quantified. Our results show that both patterns of ethanol intake during adolescence impair spatial learning, memory and cognitive flexibility in the adulthood in a dose-dependent way. Nevertheless, changes in synaptic plasticity, gene expression and levels of inactive GSK3β depended on the pattern of ethanol intake.
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Alzheimer's disease (AD) is a progressive neurodegenerative disorder without effective treatment. Accumulating evidence demonstrates the production and deposition of amyloid-β peptides (Aβ) in the pathological mechanism of this disease. ⋯ Prefrontal cortex and hippocampus amyloid-β precursor protein (APP), along with other relevant biomarkers for AD, were measured through ELISA, western blot and immunohistochemistry. Results showed that ozone ameliorated the behavioral and pathological deterioration of APP/PS1 transgenic mice, and reduced the level of APP, which supports the therapeutic potential of administration of ozone in APP/PS1 mice.
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Remarkable sex difference has been observed in emotional processing including anxiety. The hippocampus, its ventral pole in particular, modulates anxiety-like behavior in rodents. However, most researches have been performed in male animals only, leaving hippocampal modulation of anxiety in females poorly defined. ⋯ Locomotion in the open field remained similar after lesioning in either sex. More c-Fos-positive neurons were observed in the ventral hippocampus in male than in female mice after exploration in an elevated plus-maze, indicating stronger enrollment of this region in anxiety-like behavior in males. These results reveal significant biological sex difference in ventral hippocampal modulation on anxiety in mice and provide a new sight for anxiety modulation and hippocampal function.