THE BEHAVIORAL PHENOTYPE OF PITUITARY ADENYLATE-CYCLASE ACTIVATING POLYPEPTIDE-DEFICIENT MICE IN ANXIETY AND DEPRESSION TESTS IS ACCOMPANIED BY BLUNTED c-Fos EXPRESSION IN THE BED NUCLEUS OF THE STRIA TERMINALIS, CENTRAL PROJECTING EDINGER-WESTPHAL NUCLEUS, VENTRAL LATERAL SEPTUM, AND DORSAL RAPHE NUCLEUS

THE BEHAVIORAL PHENOTYPE OF PITUITARY ADENYLATE-CYCLASE ACTIVATING POLYPEPTIDE-DEFICIENT MICE IN ANXIETY AND DEPRESSION TESTS IS ACCOMPANIED BY BLUNTED c-Fos EXPRESSION IN THE BED NUCLEUS OF THE STRIA TERMINALIS, CENTRAL PROJECTING EDINGER-WESTPHAL NUCLEUS, VENTRAL LATERAL SEPTUM, AND DORSAL RAPHE NUCLEUS
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DOI:
10.1016/j.neuroscience.2011.11.046
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发表时间:
2012-01-27
期刊:
影响因子:
3.3
通讯作者:
Helyes, Z.
Helyes, Z.
中科院分区:
医学3区
文献类型:
--
作者:
Gaszner, B.;Kormos, V.;Helyes, Z.

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垂体腺苷酸环化酶激活多肽(PACAP)与应激适应(病理)生理有关。PACAP缺陷(-/-)小鼠表现出焦虑水平和抑郁样行为的改变,但对压力相关脑区的潜在机制知之甚少。因此,我们拟在明暗箱、大理石掩埋、露天和强迫游泳模式下研究PACAP(-/-)小鼠。我们还分析了强迫游泳试验诱导的c-Fos表达是否会受到以下应激相关脑区PACAP缺乏的影响:下丘脑的磁胞核和旁细胞室旁核(PVN);基底外侧(BLA)、内侧(MeA)和中央(CeA)杏仁核;终纹床核的腹侧核、背外侧核、背内侧核和卵圆形核;中隔外侧核背侧(dLS)和腹侧(vLS), Edinger-Westphal核(EWcp)中央突出,导水管周围灰质背侧(dPAG)和外侧(IPAG),中缝背核(DR)。我们的研究结果显示,与野生型相比,PACAP(-/-)小鼠的焦虑程度大大降低,运动活动增加。在强迫游泳试验中,PACAP-/-小鼠表现出抑郁样行为增加。强迫游泳暴露增加了野生型小鼠所有脑区c-Fos的表达,而在PACAP(-/-)小鼠的DR、EWcp、BSTov、BSTdl、BSTv、PVN、vLS、dPAG和IPAG中,与野生型相比,这种表达明显减弱,强烈表明它们参与了PACAP(-/-)小鼠的行为表型。PACAP缺乏不影响CeA、MeA、BSTdm和dLS的c-Fos反应。因此,我们认为PACAP对应激诱导的神经元激活具有脑区特异性作用,并可能与应激相关的情绪障碍有关。(c) 2011 ibro。Elsevier Ltd.出版。版权所有。
Pituitary adenylate-cyclase activating polypeptide (PACAP) has been implicated in the (patho)physiology of stress-adaptation. PACAP deficient (PACAP(-/-)) mice show altered anxiety levels and depression-like behavior, but little is known about the underlying mechanisms in stress-related brain areas. Therefore, we aimed at investigating PACAP(-/-) mice in light-dark box, marble burying, open field, and forced swim paradigms. We also analyzed whether the forced swim test-induced c-Fos expression would be affected by PACAP deficiency in the following stress-related brain areas: magno- and parvocellular paraventricular nucleus of the hypothalamus (PVN); basolateral (BLA), medial (MeA), and central (CeA) amygdaloid nuclei; ventral (BSTv), dorsolateral (BSTdI), dorsomedial (BSTdm), and oval (BSTov) nuclei of the bed nucleus of stria terminalis; dorsal (dLS) and ventral parts (vLS) of lateral septal nucleus, central projecting Edinger-Westphal nucleus (EWcp), dorsal (dPAG) and lateral (IPAG) periaqueductal gray matter, dorsal raphe nucleus (DR). Our results revealed that PACAP(-/-) mice showed greatly reduced anxiety and increased locomotor activity compared with wildtypes. In forced swim test PACAP-/- mice showed increased depression-like behavior. Forced swim exposure increased c-Fos expression in all examined brain areas in wildtypes, whereas this was markedly blunted in the DR, EWcp, BSTov, BSTdl, BSTv, PVN, vLS, dPAG, and in the IPAG of PACAP(-/-) mice vs. wildtypes, strongly suggesting their involvement in the behavioral phenotype of PACAP(-/-) mice. PACAP deficiency did not influence the c-Fos response in the CeA, MeA, BSTdm, and dLS. Therefore, we propose that PACAP exerts a brain area-specific effect on stress-induced neuronal activation and it might contribute to stress-related mood disorders. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.