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KMID : 1204320120280020109
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Laboratory Animal Research
2012 Volume.28 No. 2 p.109 ~ p.114
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Altered expression of γ-secretase components in animal model of major depressive disorder induced by reserpine administration
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Lee Hye-Ryun
Hwang In-Sik
Kim Ji-Eun
Choi Sun-Il
Lee Young-Ju
Goo Jun-Seo
Lee Eon-Pil
Choi Hae-Wook
Kim Hong-Sung
Lee Jae-Ho
Jung Young-Jin
Hwang Dae-Youn
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Abstract
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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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KEYWORD
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Major depressive disorder, Alzheimer's disease, reserpine, γ-secretase, APP
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