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应激和皮质酮对终纹床核中垂体腺苷酸环化酶激活肽表达的调节

Regulation of bed nucleus of the stria terminalis PACAP expression by stress and corticosterone.

作者信息

Lezak Kimberly R, Roman Carolyn W, Braas Karen M, Schutz Kristin C, Falls William A, Schulkin Jay, May Victor, Hammack Sayamwong E

机构信息

Department of Psychology, University of Vermont, 2 Colchester Avenue, John Dewey Hall, Burlington, VT, 05405, USA,

出版信息

J Mol Neurosci. 2014 Nov;54(3):477-84. doi: 10.1007/s12031-014-0269-8. Epub 2014 Mar 12.

Abstract

Single-nucleotide polymorphisms (SNPs) in the genes for pituitary adenylyl cyclase-activating peptide (PACAP) and the PAC1 receptor have been associated with stress-related psychiatric disorders. Although, from recent work, we have argued that stress-induced PACAP expression in the bed nucleus of the stria terminalis (BNST) may mediate stress-related psychopathology, it is unclear whether stress-induced increases in BNST PACAP expression require acute or repeated stressor exposure and whether increased BNST PACAP expression is related to stress-induced increases in circulating glucocorticoids. In the current work, we have used real-time quantitative polymerase chain reaction (qPCR) to assess transcript expression in brain punches from rats after stressor exposure paradigms or corticosterone injection. BNST PACAP and PAC1 receptor transcript expression was increased only after 7 days of repeated stressor exposure; no changes in transcript levels were observed 2 or 24 hours after a single-restraint session. Moreover, repeated corticosterone treatment for 7 days was not sufficient to reliably increase BNST PACAP transcript levels, suggesting that stress-induced elevations in corticosterone may not be the primary drivers of BNST PACAP expression. These results may help clarify the mechanisms and temporal processes that underlie BNST PACAP induction for intervention in stress-related anxiety disorders.

摘要

垂体腺苷酸环化酶激活肽(PACAP)基因和PAC1受体中的单核苷酸多态性(SNP)与应激相关的精神障碍有关。尽管根据最近的研究,我们认为应激诱导终纹床核(BNST)中PACAP的表达可能介导应激相关的精神病理学,但尚不清楚应激诱导的BNST中PACAP表达增加是否需要急性或反复暴露于应激源,以及BNST中PACAP表达增加是否与应激诱导的循环糖皮质激素增加有关。在当前的研究中,我们使用实时定量聚合酶链反应(qPCR)来评估应激源暴露范式或注射皮质酮后大鼠脑切片中的转录本表达。仅在反复暴露于应激源7天后,BNST中PACAP和PAC1受体的转录本表达才增加;单次束缚实验2小时或24小时后,未观察到转录水平的变化。此外,连续7天反复给予皮质酮治疗不足以可靠地增加BNST中PACAP转录本水平,这表明应激诱导的皮质酮升高可能不是BNST中PACAP表达的主要驱动因素。这些结果可能有助于阐明BNST中PACAP诱导的机制和时间过程,以便对应激相关焦虑症进行干预。

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