Neuroscience
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Cellular senescence is an important contributor to aging and age-related diseases such as Alzheimer's disease (AD). Senescent cells are characterized by a durable cell proliferation arrest and the acquisition of a proinflammatory senescence-associated secretory phenotype (SASP), which participates in the progression of neurodegenerative disorders. Clearance of senescent glial cells in an AD mouse model prevented cognitive decline suggesting pharmacological agents targeting cellular senescence might provide novel therapeutic approaches for AD. Δ133p53α, a natural protein isoform of p53, was previously shown to be a negative regulator of cellular senescence in primary human astrocytes, with clinical implications from its diminished expression in brain tissues from AD patients. ⋯ Our data suggest that Aβ-induced astrocyte cellular senescence is associated with accelerated DNA damage, and upregulation of full-length p53 and its senescence-inducing target gene p21WAF1. We also show that exogenously enhanced expression of Δ133p53α rescues human astrocytes from Aβ-induced cellular senescence and SASP through both protection from DNA damage and dominant-negative inhibition of full-length p53, leading to inhibition of Aβ-induced, astrocyte-mediated neurotoxicity. The results presented here demonstrate that Δ133p53α manipulation could modulate cellular senescence in the context of AD, possibly opening new therapeutic avenues.
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Previous studies have shown that 3-day d-amphetamine (AMPH) treatment effectively induced conditioned place preferences (CPP) and impaired pair bonding behaviors in prairie voles (Microtus ochrogaster). Using this established animal model and treatment regimen, we examined the effects of the demonstrated threshold rewarding dose of AMPH on various behaviors and their potential underlying neurochemical systems in the brain of female prairie voles. ⋯ Further, AMPH treatment decreased the number of neurons double-labeled for Egr-1 and tyrosine hydroxylase (TH) but did not affect oxytocinergic neurons in the PVN or cell proliferation and neurogenesis markers in the DG. These data not only demonstrate potential roles of the brain CRH and dopamine systems in mediating disrupted social recognition and depressive-like behaviors by AMPH in female prairie voles, but also further confirm the utility of the prairie vole model for studying interactions between psychostimulants and social behaviors.
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Cytokines and nitric oxide have been associated with impulsive and aggressive personality traits. We conducted the first study that investigated the role of SNPs in cytokines and nitric oxide genes and the influence in the progression of aggressive and impulsive behavior in 107 of cocaine and crack users. In this case-control, IL-10 (-819C/T), TNFA (-308G/A) and ENOS (-786T/C) polymorphisms were determined by Real-Time PCR. ⋯ The GA genotype (b = 0.22; p = 0.01) and the A allele (b = 0.15; p = 0.02) of -308 G/A polymorphism of the TNFA were positively correlated with aggressiveness physical. The GA genotype (b = 0.20; p = 0.03) was positively correlated with aggressiveness verbal. IL-10 (-819C/T), TNFA (-308G/A) and ENOS (-786T/C) polymorphisms might be associated with high risk of aggressive and impulsive behavior.
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Autism spectrum disorder (ASD) is a neurodevelopmental disorder displaying the modification of complex human behaviors, characterized by social interaction impairments, stereotypical/repetitive activities and emotional dysregulation. In this study, fecal microbiota transplant (FMT) via gavage from autistic children donors to mice, led to the colonization of ASD-like microbiota and autistic behaviors compared to the offspring of pregnant females exposed to valproic acid (VPA). Such variations seemed to be tightly associated with increased populations of Tenericutes plus a notable reduction (p < 0.001) of Actinobacteria and Candidatus S. in the gastrointestinal region of FMT mice as compared to controls. ⋯ Moreover, the observed FMT-dependent alterations were linked to a decrease in the methylation status. Overall, findings of the present study corroborate a key role of gut microbiota in ASD. However, further investigations are required before any possible manipulation of gut bacteria with appropriate diets or probiotics can be conducted in ASD individuals.
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Increasing evidence has shown that early life events exert long-lasting effects on brain function and mental diseases. Exercise has been proven to have many positive effects on behaviors, such as reducing anxiety- and depression-like behaviors and alleviating cognitive impairment. However, the long-lasting and even short-term effects of regular swimming exercise on social dominance remain unclear. ⋯ There was no difference between the swimming and sedentary groups in anxiety- and depression-like behaviors. Metabolomics analysis showed that there were alterations in particular metabolites and signaling pathways after one month of swimming exercise, including sphingolipid metabolism, neuroactive ligand-receptor interaction and caffeine metabolism. In conclusion, our results provide the first evidence that postweaning swimming exercise has long-lasting and sex-dependent effects on social dominance, which may be caused by metabolic adaptation.