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5-HT1A 受体结合的多样性发育与两种遗传上密切相关的近交系成年小鼠中观察到的行为差异有关。

A diverse development of 5-HT1A receptor binding is relevant to behavioral differences observed in adult mice of two genetically closely related inbred strains.

机构信息

Experimentelle Psychiatrie, Klinik für Psychiatrie und Psychotherapie, Universitätsklinikum der TU Dresden, Fetscherstraße 74, 01307 Dresden, Germany.

出版信息

Pharmacol Biochem Behav. 2010 Dec;97(2):273-8. doi: 10.1016/j.pbb.2010.08.010. Epub 2010 Aug 27.

Abstract

Only few genetic loci were supposed to be crucial for strong behavioral differences, especially in locomotion and aggression, in two closely related mice inbred strains: AB/Halle (ABH) and AB/Gatersleben (ABG). Previously we reported remarkable strain differences in 5-HT1A receptor binding in adult mice. In the present study, we were interested if the strain-specific 5-HT1A receptor binding pattern is already present very early in ontogeny which could indirectly hint at a gene that is differentially regulated in these 2 mouse strains. Since the 5-HT1A receptor is involved in the regulation of locomotion and aggression, one genetic determinate for the behavioral differences in ABH and ABG mice would have been found. Therefore, we measured [³H]8-OH-DPAT specific binding at postnatal day (PND) 1 and 21 (weanlings) using in vitro autoradiography. 5-HT1A receptor binding was not significantly different at PND 1 between strains. However, in weanlings the same 5-HT1A receptor binding pattern was observed as in adults, i.e. ABH mice display a higher forebrain 5-HT1A receptor binding compared to ABG mice. So the strain-specific forebrain 5-HT1A receptor binding pattern develops during the first 3 postnatal weeks and genetically driven mechanisms seem to be crucial. However, early environmental influences, e.g. differences in maternal care, can't be excluded.

摘要

仅有少数几个遗传基因座被认为对两种密切相关的近交系小鼠(AB/Halle [ABH]和 AB/Gatersleben [ABG])的强烈行为差异,特别是在运动和攻击行为方面,非常重要。此前,我们曾报道过成年小鼠中 5-HT1A 受体结合存在显著的品系差异。在本研究中,我们感兴趣的是,这种品系特异性的 5-HT1A 受体结合模式是否在个体发生早期就已经存在,这可能间接地暗示了在这两个小鼠品系中存在差异调控的基因。由于 5-HT1A 受体参与运动和攻击行为的调节,如果在 ABH 和 ABG 小鼠中发现了行为差异的一个遗传决定因素,那么就找到了 5-HT1A 受体。因此,我们使用体外放射自显影技术在出生后第 1 天(PND1)和第 21 天(断奶)测量了[³H]8-OH-DPAT 特异性结合。在 PND1 时,两种品系之间 5-HT1A 受体结合没有显著差异。然而,在断奶时,观察到与成年时相同的 5-HT1A 受体结合模式,即 ABH 小鼠的大脑前区 5-HT1A 受体结合高于 ABG 小鼠。因此,品系特异性的大脑前区 5-HT1A 受体结合模式在出生后前 3 周内发育,并且遗传驱动机制似乎非常重要。然而,不能排除早期环境影响,例如母性行为差异。

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