Neuroscience
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Endemic arsenism is a worldwide health problem. Chronic arsenic exposure results in cognitive dysfunction due to arsenic and its metabolites accumulating in hippocampus. ⋯ However, excessive NMDARs activity contributes to exitotoxicity and synaptic plasticity impairment. Here, we provide an overview of the mechanisms that NMDARs and their downstream signaling pathways mediate synaptic plasticity impairment due to arsenic exposure in hippocampal neurons, ways of arsenic exerting on NMDARs, as well as the potential therapeutic targets except for water improvement.
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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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Pain modulation of dopamine-producing nuclei is known to contribute to the affective component of chronic pain. However, pain modulation of pain-related cortical regions receiving dopaminergic inputs is understudied. The present study demonstrates that mice with chronic inflammatory injury of the hind paws develop persistent mechanical hypersensitivity and transient anxiety. ⋯ Furthermore, dopamine enhanced presynaptic modulation of excitatory transmission, but only in mice with inflammatory pain. High-performance liquid chromatography (HPLC) analysis of dopamine tissue concentration revealed that dopamine neurotransmitter concentration in the ACC was reduced three days following CFA. Our results demonstrate that inflammatory pain induces activity-dependent changes in excitatory synaptic transmission and alters dopaminergic homeostasis in the ACC.