Lack of trimethyltin (TMT)-induced elevation of plasma corticosterone in PACAP-deficient mice
Lack of trimethyltin (TMT)-induced elevation of plasma corticosterone in PACAP-deficient mice
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DOI：
10.1196/annals.1317.060
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发表时间：
2006-01-01
期刊：
影响因子：
--
通讯作者：
Baba, Akemichi
中科院分区：
文献类型：
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作者：
Morita, Yoshiko;Yanagida, Daisuke;Baba, Akemichi
越来越多的证据表明垂体腺苷酸环化酶激活多肽（PACAP）参与了许多应激反应。通过使用PACAP缺陷小鼠，PACAP已被证明在体内具有调节交感肾上腺轴的作用，但在调节下丘脑-垂体-肾上腺（HPA）轴中的作用尚未得到充分解决。为了阐明病理状态下内源性PACAP在HPA轴调控中的作用，研究人员给缺乏编码神经肽PACAP的Adcyap1基因（Adcyap1(-/-)）的小鼠注射三甲基锡（TMT）。三甲基锡是一种已知的神经毒素，可诱导神经元损伤和多种全身反应，包括血浆皮质酮水平升高。在野生型对照中，TMT引起水和食物摄入量的短暂减少，同时体重下降；然而，在Adcyap1（-/-）小鼠中没有观察到明显的变化。基础皮质酮水平在突变型和野生型小鼠之间无显著差异。TMT诱导野生型小鼠血浆皮质酮明显高于基础水平，但在Adcyap1（-/-）小鼠中未见显著升高。本文提示PACAP在某些病理状态下参与皮质酮的释放，但在基础状态下不参与。
Accumulating evidence implicates pituitary adenylate cyclase-activating polypeptide (PACAP) in a number of stress responses. By using PACAP-deficient mice, PACAP has been shown to have an in vivo role in the regulation of the sympathoadrenal axis, but a role in regulating the hypothalamo-pituitary-adrenal (HPA) axis has not been fully addressed. To elucidate the role of endogenous PACAP in HPA axis regulation during pathological conditions, mice lacking the Adcyap1 gene encoding the neuropeptide PACAP (Adcyap1(-/-)) were injected with trimethyltin (TMT), a neurotoxin known to induce neuronal damage and several systemic responses including elevated plasma corticosterone levels. In wild-type controls, TMT induced transient decreases in water and food intake, with a concomitant decrease in body weight; however, no significant changes were observed in Adcyap1(-/-) mice. Basal corticosterone levels were not significantly different between the mutant and wild-type mice. TMT induced a marked elevation of plasma corticosterone above basal levels in wild-type mice but no significant increase was seen in Adcyap1(-/-) mice. The present article suggests that PACAP is involved in the corticosterone release in some pathological conditions but not in the basal state.