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KMID : 0613820130230060812
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Journal of Life Science
2013 Volume.23 No. 6 p.812 ~ p.824
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Effect of Reserpine on the Behavioral Defects, Aβ-42 Deposition and NGF Metabolism in Tg2576 Transgenic Mouse Model for Alzheimer’s Disease
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Go Jun
Choi Sun-Il
Kim Ji-Eun
Lee Young-Ju
Kwak Moon-Hwa
Koh Eun-Kyoung
Song Sung-Hwa
Sung Ji-Eun
Hwang Dae-Youn
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Abstract
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Reserpine, an anti-hypertensive drug, is able to positively modulate several phenotypes associated with Aβ toxicity in a Caenorhabditis elegans model of Alzheimer’s disease (AD). We investigated into the therapeutic effects of reserpine on mammalian neurodegenerative disorders, and found that significant alteration of the key factors influencing AD was detected in Tg2576 mice after reserpine treatment for 30 days. The aggressive behavior of Tg2576 mice was significantly improved upon reserpine treatment, whereas their social contact was consistently maintained. Furthermore, the levels of Aβ-42 peptide in the hippocampus of the brain and blood serum were lower in the reserpine-treated group than in the vehicle-treated group. Among g-secretase components, the expression levels of PS-2, Pen-2, and APH-1 were slightly lower in reserpine-treated Tg2576 mice, although a significant change in nicastrin (NCT) expression was not detected. Furthermore, the serum level of nerve growth factor (NGF) increased in reserpine-treated Tg2576 mice compared with vehicle-treated mice. Among down-stream effectors of the NGF receptor TrkA signaling pathway, reserpine treatment induced elevation of TrkA phosphorylation and reduction of ERK phosphorylation. In addition, in the NGF receptor p75^NTR signaling pathway, the expression levels of p75^NTR and Bcl-2 were enhanced in reserpine-treated Tg2576 mice compared with vehicle-treated mice, whereas the expression level of RhoA declined. Overall, these results suggest that reserpine can help relieve AD pathogenesis in Tg2576 mice through downregulation of Aβ-42 deposition, alteration of r-secretase components, and regulation of NGF metabolism.
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KEYWORD
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Aβ-42, Alzheimer’s disease, r-secretase, nerve growth factor (NGF), reserpine, Tg2576 mice
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