| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Outline of Final Research Achievements |
Antidepressants are known to alter gene expression patterns by inducing changes in the epigenetic status of neuronal cells. We examined whether antidepressants exert an anti-apoptotic effect via epigenetic mechanisms. We analyzed global gene expression in mouse primary cortical neurons after treatment with antidepressants. The neuroprotection-associated genes, activating transcription factor 3 (Atf3) and heme oxygenase 1 (Hmox1), were up-regulated by treatment with amitriptyline. Quantitative chromatin immunoprecipitation assay revealed that amitriptyline increased enrichments of trimethylation of histone H3 lysine 4 in the promoter regions of Atf3 and Hmox1, which indicate an active epigenetic status. Amitriptyline pre-treatment attenuated 1-methyl-4-phenylpyridinium ion- or amyloid beta 1-42-induced neuronal cell death and inhibited the activation of extracellular signal-regulated kinase 1 and 2. These findings suggest preconditioning and neuroprotective effects of amitriptyline.
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