Study on Emotional Neuroplasticity in the Pathophysiology of Affective Disorders

由于情绪神经可塑性被报道与情绪障碍的发病机制有关，我们在应激相关障碍和抑郁症患者的动物模型中研究了神经可塑性的机制。1)应激诱导的神经可塑性改变海马神经可塑性受神经营养因子调控，在情绪记忆的发展中起作用。我们研究了新生儿隔离（NI）或NI与单一约束应激（SRS）是否会改变成年大鼠海马中几种神经营养因子的水平。NI未改变NGF、BDNF、GDNF、NT-3、IGFR1、IGFR2或IGFBP2 mRNA的水平，而NI + SRS显著下调GDNF、NGF、IGFR1和IGFBP2 mRNA的水平。提示早期不良经历可能影响由神经营养因子介导的海马神经可塑性的发育。为了进一步阐明创伤后应激障碍（PTSD）的分子病理生理机制，研究了应激条件下情境冻结（CF）对创伤后应激障碍（PTSD）的影响，并观察了应激条件下情境冻结对创伤后应激障碍海马基因表达的影响。SPS大鼠CF显著升高，cDNA微阵列分析显示vesicle associated membrane protein 2（VAMP2）水平显著升高。这些发现提示VAMP2可能参与了SPS大鼠CF的增强。3)抑郁症患者的情绪神经可塑性为了明确抑郁症患者与健康对照者情绪神经可塑性的差异，我们利用脑磁图（MEG）分析了感觉门控系统。结果表明，抑郁症患者的感觉门控系统受情绪神经可塑性的调节不同。这些结果表明，抑郁症患者的感觉门控系统的破坏可能与应激易感性相关，是情感障碍的风险。少

Since emotional neuroplasticity is reported to be associated with the pathogenesis of mood disorders, we examined the mechanism of neuroplasticity in an animal model of stress-related disorders, and patients with depression.1)Stress-induced changes in neuroplasticityHippocampal neuroplasticity regulated by neurotrophic factors, plays a role in the development of emotional memory. We examined whether neonatal isolation (NI) or NI with a single restraint stress (SRS) changed the levels of several neurotrophioc factors in the adult rat hippocampus. Whereas NI had no changes in the levels of NGF,BDNF,GDNF,NT-3,IGFR1,IGFR2, or IGFBP2 mRNA, NI + SRS significantly downregulated the levels of GDNF,NGF,IGFR1, and IGFBP2 mRNA. These findings suggest that early adverse experience may affect the development of hippocampal neuroplasticity mediated by neurotrophic factors.2)Changes in fear and hippocampal gene expression in rats subjected to a single prolonged stress (SPS), an animal model of PTSDTo … More elucidate the molecular pathophysiology of PTSD, we assessed contextual freezing (CF) after fear conditioning and examined the change in hippocampal gene expression involved in the alteration of CF in rats subjected to SPS. The SPS rats showed a significant increase in CF, and cDNA microarray analysis revealed a significant increase in the levels of vesicle associated membrane protein 2(VAMP2). These findings suggest that VAMP2 may be involved in the enhanced CF in SPS rats.3)Emotional neuroplasticity in patients with depressionTo clear the difference for emotional neuroplasticity between depressive patients and healthy controls, we have analyzed the sensory gating system used by Magnetoencepharography(MEG). As a result, depressed patients had the different modulation in sensory gating system by emotional neuroplasticity. These results suggest that the broken sensory gating system in depressed patients might be correlated with vulnerability for stress as the risk for affective disorders. Less