老齢マウスにおけるドパミン神経関連遺伝子のmRNA発現量変化

• Published in: 日本薬理学会年会要旨集 p. 3-P-262
• Main Authors: 高田, 芙友子, 田代, 恵麗, 福永, 裕子, 岩尾, 卓朗, 道具, 伸也
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2022
• Subjects: aging; brain; dopaminergic system; neurodegeneration
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.95.0_3-P-262

Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra. It is well known that PD is one of the most common age-related neurodegenerative disease and a multifactorial disorder including aging, genetic and environmental factors. Although the prevalence of PD is increased with age, it remains unclear how aging affects dopaminergic neurons and expression of proteins that contribute to PD. Here, we performed real-time PCR analysis of whole brains obtained from male C57BL/6 mice at the age of 8, 32, 52 and 108 weeks to clarify age-related changes in expression of genes involved in PD and age at the onset of age-related changes. In genes expressed in dopaminergic neurons, mRNA expression levels of Th (tyrosine hydroxylase), Slc6a3 (dopamine transporter 1, DAT1), Slc18a2 (vesicular monoamine transporter 2, VMAT2) and Drd2 (dopamine receptor D2) were decreased with age. Th and Drd2 mRNA were significantly decreased in 52-week-old mice. Among the 4 PD-related genes (Atp13a2, Lrrk2, Park2 and Pink1) examined in this study, Atp13a2 and Pink1 mRNA were significantly decreased in 52-week-old mice. These findings suggest that aging-induced changes in the mRNA expression of dopaminergic neuron-related genes may occur in middle-aged brain. These normal aging-induced changes in mRNA expression could contribute to the onset and progression of PD.