Early parental deprivation in the marmoset monkey produces long-term changes in hippocampal expression of genes involved in synaptic plasticity and implicated in mood disorder.
Early parental deprivation in the marmoset monkey produces long-term changes in hippocampal expression of genes involved in synaptic plasticity and implicated in mood disorder.
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DOI：
10.1038/npp.2008.106
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发表时间：
2009-05
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影响因子：
--
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中科院分区：
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在情绪障碍中，包括父母分离在内的早期应激源是易感因素，海马区参与是突出的。在普通的绒猴中，婴儿时期的日常父母剥夺会产生一种亲抑郁状态，压力系统中的基础活动和反应性增加，轻度快感缺失至少会持续到青春期。在这里，我们检查了8个基因的表达，每个基因都与神经可塑性和情绪障碍的病理生理学有关，在这些相同的青少年绒猴的海马体中，相对于它们正常饲养的兄弟姐妹对照组。我们还测量了海马体体积。早期剥夺导致大鼠海马区GAP-43mRNA、5-HT1A型受体和5-HT1AR结合量([~3H]WAY100、635)减少，VGAT基因表达增加。脑源性神经营养因子、突触素、VGluT1、MAP2和刺激素转录本没有变化。与体内生化和行为学指标有一定的相关性，其中VGluT1mRNA与奖赏行为相关，5-HT1AR与脑脊液皮质醇相关。早期剥夺并不影响海马体体积。我们的结论是，在没有后续应激源的情况下，非人类灵长类动物的早期剥夺对海马区突触功能和可塑性相关基因的表达有长期影响。GAP-43和5-HT1AR表达的减少与情绪障碍的研究结果相当，支持后者反映了疾病易感性的早期发育贡献的可能性。同样，否定的结果表明，情绪障碍的其他特征，如海马体体积减少和BDNF表达，与病理生理过程的不同方面有关。
In mood disorder, early stressors including parental separation are vulnerability factors, and hippocampal involvement is prominent. In common marmoset monkeys, daily parental deprivation during infancy produces a pro-depressive state of increased basal activity and reactivity in stress systems and mild anhedonia that persists at least to adolescence. Here we examined the expression of eight genes, each implicated in neural plasticity and in the pathophysiology of mood disorder, in the hippocampus of these same adolescent marmosets, relative to their normally-reared sibling controls. We also measured hippocampal volume. Early deprivation led to decreases in hippocampal GAP-43 mRNA, 5-HT1A receptor mRNA and 5-HT1AR binding ([3H]WAY100,635), and to increased VGAT mRNA. BDNF, synaptophysin, VGluT1, MAP2, and spinophilin transcripts were unchanged. There were some correlations with in vivo biochemical and behavioural indices, including VGluT1 mRNA with reward-seeking behaviour, and 5-HT1AR mRNA with CSF cortisol. Early deprivation did not affect hippocampal volume. We conclude that early deprivation in a non-human primate, in the absence of subsequent stressors, has a long-term effect on the hippocampal expression of genes implicated in synaptic function and plasticity. The reductions in GAP-43 and 5-HT1AR expression are comparable with findings in mood disorder, supporting the possibility that the latter reflect an early developmental contribution to disease vulnerability. Equally, the negative results suggest that other features of mood disorder, such as decreased hippocampal volume and BDNF expression, are related to different aspects of the pathophysiological process.
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