Study on the molecular mechanism of psychiatric disorders that targets PACAP signaling pathways and aimed at the development of therapeutic drug
Description: Pathophysiological mechanisms for psychiatric disorders remain poorly understood, which need to be urgently addressed. Recent studies have suggested that PACAP is implicated in neuropsychological functions and the risk and pathogenesis of psychiatric disorders. In this study, in order to obtain insights relevant to drug development, we examined brain signaling pathways as well as intracellular signaling pathways that are relevant to PACAP-dependent signaling. We obtained the data showing that the implication of noradrenaline in PACAP-deficient mouse phenotypes, involvement of BDNF signaling in PACAP-dependent axon outgrowth, necessity of β-arrestin2 for PACAP-induced 5-HT2A receptor internalization, and interaction and internalization of PACAP receptor PAC1 with β-arrestin2, which induces prolonged ERK1/2 activation. The present observations as well as the assay systems generated are expected to contribute to future drug discovery research.
Amount: ¥16,900,000
Funding type: research
Funder scheme: Grant-in-Aid for Scientific Research (B)
Start date: 2014-04-01
End date: 2018-03-31
Investigator: Hitoshi Hashimoto
Institution: Osaka University
Funded outputs count: 55
Funder award ID: 26293020
OpenAlex ID: G7109057272