Reduced gene expression for Kv9.3 potassium channel subunit and cortical dysfunction in schizophrenia

2016 Fiscal Year Final Research Report

• Project/Area Number: 25293247
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Kanazawa University
• Principal Investigator: Hashimoto Takanori 金沢大学, 医学系, 准教授 (40249959)
• Co-Investigator(Kenkyū-buntansha): 戸田 重誠 金沢大学, 大学病院, 講師 (00323006) ; 吉原 亨 京都大学, 医学(系)研究科(研究院), 助教 (00401935) ; 上田 なつ子 (辻野) 筑波大学, 国際統合睡眠医学研究機構, 助教 (40432166)
• Research Collaborator: Lewis David A University of Pittsburgh, Department of Psychiatry and Neuroscience
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: ヒト死後脳 / 霊長類モデル / 遺伝子改変マウス

Outline of Final Research Achievements

In the prefrontal cortex (PFC) of subjects with schizophrenia, alterations in parvalbumin (PV)-containing neurons are thought to contribute to cognitive deficits. Kv9.3 is a potassium channel subunit that is selectively expressed in PV neurons and critical to their roles in cognitive functions. Our cellular level quantification of the mRNA levels for KCNS3, the gene encoding Kv9.3, revealed that the number of KCNS3 mRNA-expressing neurons and the mRNA level per neuron were significantly reduced in the PFC of schizophrenia subjects. KCNS3 mRNA levels were unaffected in the PFC of monkeys exposed to antipsychotics, indicating that the lower KCNS3 expression is not solely due to the antipsychotic treatment. To test the effect of lower Kv9.3 subunit expression on cognitive functions, we inactivated the kcns3 gene in mice and confirmed reduced kcns3 mRNA expression in the PFC of these mice.

Free Research Field

統合失調症の病態生理