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Study on early environment-induced neuronal network which is involved in vulnerability to psychiatric disorders

早期环境诱发的神经元网络与精神疾病易感性的研究

基本信息

批准号：
16390321
负责人：
KANBA Shigenobu
金额：
$ 9.41万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

The present study aimed to elucidate the mechanism behind the stress vulnerability that results from its impairment, and to thereby contribute to the development of prevention methods. Therefore, both behavioral and neurochemical techniques were used to determine the mechanisms relating to the structure and function of neuron networks involved in the control of emotion.Better early environment induced increase in neurogenesis in response to stress (Kanba et al.,2005). Ginseng saponin was found to increase neurogenesis and thus was supposed to have antistress effects (Quia et al.,2005). It has been suggested that the action of antidepressants may be related to the promotion of hippocampal neurogenesis. Herein, as a model of vulnerability to depression, we investigated the effects of administration of cytokine hIFN-α, which is known to induce depression, on hippocampal neurogenesis. The results showed that hIFN-Hospital administration induced astroglia-mediated IL-1β production in the hi … More ppocampus and reduced neurogenesis (Kaneko et al.,2006). Based on these findings, the mechanism of the central action of hIFN-Hospital was partially elucidated. These results also supported the aforementioned possibility that inhibition of hippocampal neurogenesis may be involved in cognitive vulnerability to depression, an idea that had previously been assumed only from the perspective of the mechanism of antidepressants.The relationship between emotional memory and neurochemical function was investigated in elderly rats, which have reduced hippocampal function. The results showed that the stress response of phosphorylated CREB, a signaling molecule, was attenuated in elderly rats. In addition, although neurogenesis occurs in the dentate gyrus of the hippocampus, the stress response of this neurogenesis was also reduced in elderly rats (Kudo et al.,2005;Wati et al.,2006). These changes may possibly explain vulnerability to psychiatric disease.Catecholamine activity in prefrontal cortex is regulated through AMPA/kainite receptors. Antipsychotics are found to inhibit desensitization of the receptors. Our study showed a new possibility of antistress drugs which act on AMPA receptors (Kuroki et al.,2007). Less

本研究旨在阐明其受损导致的应激脆弱性背后的机制，从而有助于预防方法的发展。因此，使用行为和神经化学技术来确定与参与情绪控制的神经元网络的结构和功能相关的机制。2005年）。人参皂苷被发现增加神经发生，因此被认为具有抗应激作用（Quia等人，2005年）。有研究表明，抗抑郁药的作用可能与促进海马神经发生有关。在此，作为抑郁症易感性的模型，我们研究了给予已知可诱导抑郁症的细胞因子hIFN-α对海马神经发生的影响。结果显示，hIFN-α诱导星形胶质细胞介导的IL-1β产生。 ...更多信息海马和减少的神经发生（Kaneko等人，2006年）。基于这些发现，hIFN-Hospital的中枢作用机制被部分阐明。这些结果也支持了上述的可能性，即海马神经发生的抑制可能与抑郁症的认知脆弱性有关，这是以前仅从抗抑郁药的机制的角度假设的观点。在海马功能降低的老年大鼠中，研究了情绪记忆和神经化学功能之间的关系。结果表明，老年大鼠磷酸化CREB信号分子的应激反应减弱。此外，尽管神经发生发生在海马的齿状回中，但这种神经发生的应激反应在老年大鼠中也减少（Kudo等人，2005;Wati等人，2006年）。这些变化可能解释了精神疾病的易感性。前额叶皮质中的儿茶酚胺活性通过AMPA/红藻氨酸受体调节。抗精神病药被发现抑制受体的脱敏。我们的研究显示了作用于AMPA受体的抗应激药物的新的可能性（Kuroki等人，2007年）。少