Study on molecular mechanism for telomere shortening induced by stress exposure on schizophrenia

2017 Fiscal Year Final Research Report

• Project/Area Number: 26870878
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology; Neurochemistry/Neuropharmacology
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: TORIUMI Kazuya 公益財団法人東京都医学総合研究所, 精神行動医学研究分野, 主任研究員 (10549421)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: テロメア / 統合失調症 / 抗精神病薬 / 神経新生

Outline of Final Research Achievements

First, we found that leukocyte telomere length in Japanese patients with schizophrenia was shorter than that in healthy subjects. Second, we recognized that subchronic treatment of second-generation antipsychotics such as Risperidone (RIS), but not first-generation antipsychotics, elevated brain-derived neurotrophic factor level via 5-HT2A antagonism and increased telomerase (TERT) expression in the hippocampus. Finally, RIS improved the telomere shortening in a telomerase activity-dependent manner, the impairment of adult neurogenesis in the dentate gyrus, and some behavioral deficits shown in the mice exposed social isolation rearing stress. These findings suggested that the therapeutic effects of RIS might be mediated by telomerase activation, probably via the enhanced neurogenesis in the dentate gyrus. Furthermore, decrease of telomerase activity might be related to negative symptom, cognitive impairment, and prepulse inhibition deficits, but not positive symptom.

Free Research Field

神経精神薬理