Neuroscience
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Maternal opioids abuse has some deleterious consequences on next generations. Besides, children's rearing conditions can affect the behavioral states and brain plasticity in their later life. In the present study, we investigated the effects of maternal morphine (MOR) treatment and post-weaning rearing conditions on memory, pain threshold, and the ventral striatum dopaminergic activity in male offspring. ⋯ At molecular level, maternal MOR injections and social isolation reduced DA levels and altered expressions of D1R, D2R, and DAT within the ventral striatum of these male offspring. However, post-weaning EE partially buffered these changes. Our finding signified the effects of maternal MOR exposure and social isolation on the behaviors and neurochemistry of brain in next generation, and it also provided evidence on reversibility of these alterations following EE.
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By the effort to identify candidate signaling molecules important for the formation of robust circadian rhythms in the suprachiasmatic nucleus (SCN), the mammalian circadian center, here we characterize the role of α2δ proteins, synaptic molecules initially identified as an auxiliary subunit of the voltage dependent calcium channel, in circadian rhythm formation. In situ hybridization study demonstrated that type 3 α2δ gene (α2δ3) was strongly expressed in the SCN. ⋯ Cultured SCN slices from Per1-luc transgenic Cacna2d3-/- mice revealed reduced synchrony of Per1-luc gene expression rhythms among SCN neurons. These findings suggest that α2δ3 is essential for synchronized cellular oscillations in the SCN and thereby contributes to enhancing the sustainability of circadian rhythms in behavior.
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Poststroke depression (PSD) is a common complication of stroke and has long been a serious threat to human health. PSD greatly affects neurological recovery, quality of life and mortality. Recent studies have shown that 5-hydroxymethylcytosine (5hmC), an important epigenetic modification, is enriched in the brain and associated with many neurological diseases. ⋯ In particular,DhMRs were strongly enriched in genes with lymphoid enhancer factor 1 (LEF1) binding motifs. Finally, we demonstrated that decreases in TET2 expression in the brain caused PSD by decreasing Wnt/β-catenin/LEF1 pathway signaling to promote inflammatory factor IL-18 expression. In conclusion, our data highlight the potential for 5hmC modification as a therapeutic target for PSD.
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Despite the high prevalence of major depressive disorder (MDD), understanding of the biological underpinnings remains limited. Rodent models suggest that changes in activity and output of dopamine (DA) neurons in the ventral tegmental area (VTA) are important for depressive-like phenotypes. Additionally, brain inflammatory processes are thought to contribute to MDD pathology and inflammation in the VTA has been linked to changes in VTA DA neuronal activity. ⋯ In contrast, IL-1β expression was unchanged in male or female mice following SCVS. No significant increases in VTA ionized calcium binding adapter molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP) immunochemistry were detected following CSDS that would be indicative of a robust inflammatory response. In conclusion, we show that chronic stressors distinctively alter expression of proinflammatory genes in the VTA and changes may depend on the severity and time-course of the stress exposure.
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Transglutiminase-2 (TG2) is a multifunctional enzyme that has been implicated in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS) using global knockout mice and TG2 selective inhibitors. Previous studies have identified the expression of TG2 in subsets of macrophages-microglia and astrocytes after EAE. The aims of the current investigation were to examine neuronal expression of TG2 in rodent models of chronic-relapsing and non-relapsing EAE and through co-staining with intracellular and cell death markers, provide insight into the putative role of TG2 in neuronal pathology during disease progression. ⋯ TG2 induction occurred concurrently with the upregulation of the blood vessel permeability factor and angiogenic molecule Vascular Endothelial Growth Factor (VEGF). Extracellular TG2 was found to juxtapose with fibronectin, within and surrounding blood vessels. Though molecular and pharmacological studies have implicated TG2 in the induction and severity of EAE, the cell autonomous functions of this multifunctional enzyme during disease progression remains to be elucidated.