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2013 Fiscal Year Final Research Report

Gene Exression in the Substantina Nigra of Subjects with Schizophrenia

Research Project

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Project/Area Number 24659539
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Psychiatric science
Research InstitutionKanazawa University

Principal Investigator

HASHIMOTO TAKANORI  金沢大学, 医学系, 准教授 (40249959)

Co-Investigator(Kenkyū-buntansha) TODA Shigenobu  金沢大学, 大学病院, 講師 (00323006)
Project Period (FY) 2012-04-01 – 2014-03-31
Keywords脳神経疾患 / 死後脳研究
Research Abstract

We tested our hypothesis that GABA neurotransmission by projection neurons in the substantia nigra pars reticulata (SNR) is reduced and dopamine neurons in the substantia nigra pars compacta (SNC) are hyperactive as the result. We analyzed gene expression for GAD67, an enzyme for GABA synthesis, tyrosine hydroxylase (TH), an enzyme for dopamine synthesis, and KCNS3 voltage-gated potassium channel subunit in the SNR and SNC of 14 pairs of control and sex- and age-matched schizophrenia subjects, using in situ hybridization. In the SNR, GAD67 mRNA levels did not differ between control and schizophrenia subjects. In contrast, TH and KCNS3 mRNA levels were significantly lower in the SNC of schizophrenia subjects. Our results did not support altered GABA neurotransmission by SNR neurons. However, decreased KCNS3 expression could enhance excitability of SNC dopamine neurons, contributing to positive symptoms. Lower TH levels might reflect a compensatory mechanism.

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Published: 2015-06-25  

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