KUROKI Toshihide Kyushu University, Graduate School of Medical Sciences, Associate Professor, 医学研究院, 助教授 (60215093)
KAWASAKI Hiroaki Kyushu University, Hospital, Assistant Professor, 大学病院, 講師 (50224762)
MONJI Akira Kyushu University, Hospital, Assistant Professor, 大学病院, 講師 (00294942)
|Budget Amount *help
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2006: ¥100,000 (Direct Cost: ¥100,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥13,200,000 (Direct Cost: ¥13,200,000)
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
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