儿童青少年抑郁严重危害未成年人身心健康和生命安全，且病因和发病机制迄今不清。课题组前期研究首次发现，儿童青少年抑郁患者血浆肌苷水平显著降低，且动物模型腹腔注射肌苷后可缓解抑郁样行为。最近研究报道，MAPK/ERK信号通路与成人抑郁发病密切相关，但国内外尚无该通路参与儿童青少年抑郁相关报道。因此，本项目以青幼期抑郁大鼠模型为载体,以肌苷介导MAPK/ERK信号通路为研究主线，探索儿童青少年抑郁发病机制及干预靶点。拟开展以下工作：①从蛋白和基因层面证实MAPK/ERK通路在青幼期抑郁大鼠中的改变，寻找该通路的关键蛋白和表达的关键脑区；②在青幼期抑郁大鼠腹腔注射肌苷，测定脑区肌苷含量和MAPK/ERK通路的关键蛋白表达的变化，并评价行为学改变；③进一步在关键蛋白表达脑区注射MAPK/ERK通路的关键蛋白拮抗剂后，观察其行为学改变，进一步验证肌苷通过MAPK/ERK通路调控青幼期大鼠的抑郁样行为。

Children and adolescents depression seriously endanger their physical and mental health and lives of juveniles, while its etiology and pathogenesis is still not clear. Our previous studies first found that the plasma levels of inosine in patients with children and adolescents depression are significantly more than health controls. And, after intraperitoneal injection of the inosine in the depressed animal model, we found their depressive-like behavior have been relieved. Recent studies reported that MAPK / ERK signaling pathway is significantly associated with the pathogenesis of adult depression, but there is no report for children and adolescents depression.Thus, based on the rats model in childhood depression and the MAPK/ERK signal pathway, the aim of this study was to investigate the pathogenesis of depression in children and adolescents, and to explore their potential therapeutic target. We plan to carry out the following work: ① we will confirm the changes of MAPK/ERK pathway in childhood rats from both of the protein and gene level, and look for the key protein and key brain areas of this pathway; ②After intraperitoneal injection of inosine in childhood depressed rats, we will determine the inosine content in their brain and evaluate animals’ behavioral changes, as well as detect the expression of key protein of MAPK/ERK pathway; ③the key protein antagonists of MAPK / ERK pathway will be injected into the key brain area and we will further investigate the inhibitory effect of inosine on MAPK/ERK pathway in childhood depressed rats according to their behavioral analysis.