Altered expression of γ-secretase components in animal model of major depressive disorder induced by reserpine administration

利血平诱导的重度抑郁症动物模型中γ-分泌酶成分表达改变

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作者:Hye-Ryun Lee, In-Sik Hwang, Ji-Eun Kim, Sun-Il Choi, Young-Ju Lee, Jun-Seo Goo, Eon-Pil Lee, Hae-Wook Choi, Hong-Sung Kim, Jae-Ho Lee, Young-Jin Jung, Dae-Youn Hwang

Abstract

Altered expression of neurotrophic factors as well as neuroinflammation is commonly associated with Major depressive disorder (MDD) and Alzheimer's disease (AD). To investigate whether or not reserpine-induced MDD affects the expression of AD-related proteins, the expression of γ-secretase components and substrate were measured in brains of ICR mice following reserpine treatment for 15 days. In active avoidance test, total response time and peak slightly increased in the 2 mg/kg reserpine (RSP2)-treated group compared to vehicle-treated group (P<0.05). Expression and phosphorylation of MKP-1, which is a key factor in MDD pathology, were both higher in the RSP2-treated group than the vehicle- and 1 mg/kg reserpine (RSP1)-treated groups (P<0.02). Furthermore, full-length expression of amyloid precursor protein (APP) was enhanced in the RSP1 and RSP2-treated groups compared to the vehicle-treated group, whereas expression of γ-secretase components decreased (P<0.03). Among the three components of the γ-secretase complex, nicastrin protein underwent the largest decrease in expression, as detected by Western blotting (P<0.03). Therefore, the data presented here provide additional evidence about the pathological correlation between MDD and AD.

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