憂鬱症是嚴重影響現代人身心健康的疾病，嚴重者甚至會使患者有自殺傾向。在過去的研究裡指出，憂鬱症患者的海馬迴(hippocampus) 體積有萎縮現象。這個現象可能是來自於神經新生(neurogenesis) 現象下降，現有神經細胞凋亡，或是神經細胞的型態改變。其中，神經新生現象是近代研究憂鬱症的重要議題。
過去我們實驗室利用習得無助 (learned helplessness) 憂鬱症模式的老鼠，研究憂鬱症與神經新生的相關性，發現在習得無助老鼠背側海馬迴 (dorsal hippocampus) 的神經新生現象，明顯比對照組老鼠低。為了進一步了解習得無助老鼠在此腦區發生的
分子機制改變，我們做了對照組、習得無助老鼠及非習得無助老鼠 (non-learned helplessness) 在腹側以及背側海馬齒狀回 (dentate gyrus) 的DNA 微陣列，來比較基因表現的變化。經由結果分析，發現習得無助老鼠的背側海馬齒狀回，γ-胺基丁酸 (γ-aminobutyric acid, GABA) 的傳導以及受體的活性有改變，此外還有神經傳導作用、離子通道和纖維母細胞生長因子訊息調控的改變；我們可藉由進一步的研究，了解這些改變是否與憂鬱症的致病機制有關。在非習得無助老鼠的腹側海馬齒狀回也發現了神經保護機制的啟動，以及基因 transthyretin 的高度表現。這些神經保護機制以及基因，或許在幫助老鼠經過電擊的壓力後，仍不致產生憂鬱症行為扮演了重要的角色。
此外，我們也利用習得無助憂鬱症動物模式，觀察了腹、背側海馬齒狀回，腦神經滋養因子 (BDNF) 及其受體 (p75NTR) 的蛋白質表現量。結果顯示習得無助老鼠背側海馬齒狀回的神經滋養因子顯著下降，與先前觀察到的神經新生現象下降相吻合。

Previous studies have indicated that high percentage of recurrent major depression patients have hippocampal atrophy. It could be caused not only by the atrophy of existing neurons but also by a reduction of adult hippocampal neurogenesis in dentate gyrus. Thus, the role of neurogenesis in major depression pathophysiology has raised great interest in recent years.
From past experiments in our laboratory using learned helplessness animal model of depression, we had found a reduction in adult neurogenesis in the dorsal hippocampus of rats showing learned helplessness behavior. In order to identify the underlying molecular mechanisms for the reduced neurogenesis in dorsal hippocampus, we conducted DNA microarray analysis in dorsal and ventral dentate gyrus of learned helpless, nonhelpless, and control rats. According to gene ontology analysis, we found differentially expressed genes involved in negative regulation of neuroblast proliferation and neurogenesis in LH dorsal, LH ventral and NoLH ventral DG, whereas the neuroprotection was also found in NoLH ventral DG. The GABA related transmission and receptor activity, channel activity, neurotransmission, and fibroblast growth factor
receptor signaling pathway were regulated in LH dorsal DG compared to control.
In addition to the genetic study, we also found that the protein expression levels of mature- and pro-BDNF were down-regulated in the dorsal DG of LH rats, which was
corresponds well with the reduced neurogenesis. Further investigation of candidate genes, pathways and regulation of neurotrophic factors are valuable for finding the crucial mechanisms involved in depression pathology.

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