Analysis of cognitive behavioral disorders induced by neurotrophic factor in developmental dopaminergic neuron

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K07989
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pharmacology in pharmacy
• Research Institution: Institute for Developmental Research, Aichi Human Service Center
• Principal Investigator: MIZUNO MAKOTO 愛知県心身障害者コロニー発達障害研究所, 神経制御学部, 主任研究員 (20345515)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 発達障害

Outline of Final Research Achievements

Epidermal growth factor (EGF) is protein factors which enhance survival, maintenance and neurite outgrowth of midbrain dopaminergic neurons. To evaluate a potential neuroinflammatory role of the EGF, we examined the neurobehavioral consequences of EGF administration as well as its effects on inducible prostaglandin synthetase (cyclooxygenase 2; Cox-2) expression in mice. Neuroinflammation is also implicated in a number of developmental disorders. Inducing of EGF to mice showed social behavioral abnormalities which are related with enhances of the expression of Cox-2. However mice with social behavioral dysfunction exhibited normal locomotor and learning activities and normal expression levels of dopaminergic neuron related proteins and dopamine metabolism. We conclude this EGF-triggered neuroinflammatory process is mediated in part by Cox-2 activity in developmental stages of around postnatal day14 to generate neurobehavioral abnormalities.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

脳内炎症はこれまで多くの場合、変性疾患において神経細胞死との関係で研究がなされてきたが脳内炎症が神経変性を伴うことなくプロスタグランジンが脳神経機能を修飾し、結果として社会性行動変化をもたらした研究結果は、神経変性疾患にともなう伴う認知行動障害は神経細胞の数的変化だけではなく、機能変化で一部は説明できる可能性を示唆した。社会性障害に対するシクロオキシゲナーゼの脳内で発現が変化し、それに伴い行動障害が見られる時期が明らかになり起因時期から障害発症期までに対処法を考える可能性が出来る。