Novel approaches to drug development of schizophrenia
Description: We generated a model mouse that mimics the nutritional deficiency during brain development and showed that the mice exhibit schizophrenia-like phenotypes. We also revealed that dysfunction of the nuclear receptor PPARA, which uses fatty acids as endogenous ligands, may cause the risk of the phenotypes in this animal (Maekawa et al., 2017). Furthermore, we identified four variants of the PPARA gene are associated with functional changes in patients with schizophrenia. Additionally, we reported that Ppara knockout mice show schizophrenia-like behavioral changes and exhibit synaptic morphology changes similar to those observed in postmortem brains of individuals with schizophrenia. In addition, we found that PPARA agonists improved the phenotype of a drug-induced model mouse of schizophrenia (Wada, Maekawa et al., 2020). These results indicate that PPARa dysfunction is involved in the pathophysiology of schizophrenia and it shows that PPARa is a new therapeutic target for schizophrenia.
Amount: ¥4,550,000
Funding type: research
Funder scheme: Grant-in-Aid for Scientific Research (C)
Start date: 2018-04-01
End date: 2023-03-31
Investigator: Motoko Maekawa
Institution: Tohoku University(2021-2022)Institute of Physical and Chemical Research(2018-2020)
Subfield: Molecular Biology
Domain: Life Sciences
Funded outputs count: 13
Funder award ID: 18K07578
OpenAlex ID: G7715329105