![]() Setting National Institutes of Health Animal Center. Animals were genotyped for −1002 T > G, and the data were analyzed using analysis of variance. Animals were exposed to repeated social separation stress and tested for individual differences in alcohol consumption. Levels of NPY in cerebrospinal fluid were measured by radioimmunoassay, and messenger RNA levels were assessed in the amygdala using real-time polymerase chain reaction. We performed gel shift assays using nuclear extract from testes, brain, and hypothalamus. Objective To determine whether functional NPY variation influences behavioral adaptation to stress and alcohol consumption in a nonhuman primate model of early adversity (peer rearing).ĭesign We sequenced the rhesus macaque NPY locus (rh NPY) and performed in silico analysis to identify functional variants. Genetic variation that affects the NPY system could moderate stress resilience and susceptibility to alcohol dependence. In humans, low NPY expression predicts amygdala response and emotional reactivity. Shared Decision Making and CommunicationĬontext Neuropeptide Y (NPY) counters stress and is involved in neuroadaptations that drive escalated alcohol drinking in rodents.Scientific Discovery and the Future of Medicine.Health Care Economics, Insurance, Payment.Clinical Implications of Basic Neuroscience.Challenges in Clinical Electrocardiography.D, NPY messenger RNA (mRNA) expression in the amygdala as a function of the −1002 T > G allele ( P < .001 T/T, n = 4 G carrier, n = 8). Open arrowheads indicate bands that increase with G allele probes, and closed arrowheads indicate that which shows a relative increase with T allele probes. Relative migrations of the protein molecular weight standards are shown. C, Gel shift assay results from experiments performed using nuclear extracts from whole-brain tissue, osteosarcoma cells (MG-63), and glucocorticoid-treated hypothalamic cells (IVB cells treated with dexamethasone ). Binding sites (shown in dashed lines Sox5 and a preferred glucocorticoid response element half-site) were predicted to be disrupted by the −1002 T > G SNP. Predicted sites for transcription factor binding (above) and sequence conservation among primates (below, black indicates conserved) are shown. The precise locations of the −1002 T > G SNP (in bold) and the oligonucleotide sequence used in the gel shift assays (underlined) are indicated. B, Region 40 base pairs upstream and downstream of the −1002 T > G SNP. A, A schematic of NPY, regulatory region, and single-nucleotide polymorphisms (SNPs) detected by sequencing of genomic DNA. Rhesus NPY −1002 T > G is present in a conserved portion of an NPY repressor and results in altered DNA-protein interactions and decreased amygdala NPY expression. ![]()
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