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

本研究旨在阐明其损伤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，行为和神经化学技术都被用来确定与情绪控制相关的神经元网络的结构和功能相关的机制。更好的早期环境会诱导应激反应中神经发生的增加（Kanba et al.,2005）。人参皂苷被发现可以增加神经发生，因此被认为具有抗应激作用（Quia 等，2005）。有人提出，抗抑郁药的作用可能与促进海马神经发生有关。在此，作为易患抑郁症的模型，我们研究了已知会诱发抑郁症的细胞因子 hIFN-α 的施用对海马神经发生的影响。结果表明，hIFN-Hospital 给药诱导了 hi ppocampus 中星形胶质细胞介导的 IL-1β 的产生，并减少了神经发生（Kaneko et al.,2006）。基于这些发现，hIFN-Hospital的中枢作用机制得到部分阐明。这些结果也支持了上述可能性，即海马神经发生的抑制可能与抑郁的认知脆弱性有关，这一观点以前仅从抗抑郁药的机制角度假设。在海马功能下降的老年大鼠中研究了情绪记忆与神经化学功能之间的关系。结果表明，磷酸化信号分子CREB的应激反应在老年大鼠中减弱。此外，虽然神经发生发生在海马齿状回，但老年大鼠中这种神经发生的应激反应也有所减少(Kudo et al.,2005;Wati et al.,2006)。这些变化可能解释了对精神疾病的脆弱性。前额皮质中的儿茶酚胺活性通过 AMPA/kainite 受体进行调节。发现抗精神病药可以抑制受体的脱敏。我们的研究显示了作用于 AMPA 受体的抗应激药物的新可能性（Kuroki 等，2007）。较少的

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