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このアイテムの引用には次の識別子を使用してください: http://hdl.handle.net/10564/4352

タイトル: Amino acid transporter Asc-1 (SLC7A10) expression is altered in basal ganglia in experimental Parkinsonism and L-dopa-induced dyskinesia model mice
その他のタイトル: パーキンソン病モデルマウス及び L-dopaによってジスキネジアを誘導したモデルマウスは大脳基底核においてアミノ酸トランスポータであるASC-1の発現が変化する
著者: Nakahara, Kazuki
Okuda, Hiroaki
Isonishi, Ayami
Kawabe, Yoshie
Tanaka, Tatsuhide
Tatsumi, Kouko
Wanaka, Akio
キーワード: Amino acid transporter Asc-1 (SLC7A10)
Basal ganglia
6-hydroxydopamine (6-OHDA)
Parkinson’s disease (PD)
L-dopa-induced dyskinesia (LID)
Laser microdissection
発行日: 2023年1月
出版者: Elsevier B.V.
引用: Journal of Chemical Neuroanatomy. 2023 Jan, vol.127, article no.102191
抄録: In Parkinson's disease (PD), a decrease in dopamine levels in the striatum causes abnormal circuit activity in the basal ganglia, resulting in increased output via the substantia nigra pars reticulata (SNr). A characteristic feature of glutamatergic synaptic transmission in the basal ganglia circuitry under conditions of dopamine depletion is enhanced synaptic activity of NMDA receptors. However, the cause of this NMDA receptor hyperactivity is not fully understood. We focused on Asc-1 (SLC7A10), an alanine–serine–cysteine transporter, as one of the factors that regulate NMDA receptor activity by modulating D-serine and glycine concentration in synaptic clefts. We generated PD model mice by injection of 6-hydroxydopamine into the unilateral medial forebrain bundle and analyzed the expression level of Asc-1 mRNA in the nuclei of basal ganglia (the external segment of the globus pallidus (GPe), subthalamic nucleus (STN), and SNr) compared to control mice. Each nucleus was dissected using laser microdissection, and RNA was extracted and quantified by quantitative PCR. Asc-1 mRNA expression was significantly higher in the GPe and lower in the SNr under the PD state than that in control naïve mice. The STN showed no change in Asc-1 mRNA expression. We further modeled L-dopa-induced dyskinesia by administering L-dopa continuously for 14 days to the PD model mice and found that Asc-1 mRNA expression in the GPe and SNr became close to that of control mice, regardless of the presence of abnormal involuntary movements. The present study revealed that Asc-1 mRNA expression is differentially regulated in the basal ganglionic nuclei in response to striatal dopamine concentration (depleted or replenished) and suggests that Asc-1 can be a therapeutic target for the amelioration of motor symptoms of PD.
内容記述: 権利情報:© 2022 Elsevier B.V. All rights reserved.
URI: http://hdl.handle.net/10564/4352
ISSN: 0891-0618
DOI: https://doi.org/10.1016/j.jchemneu.2022.102191
学位授与番号: 24601甲第901号
学位授与年月日: 2024-03-14
学位名: 博士(医学)
学位授与機関: 奈良県立医科大学
出現コレクション:2023年度

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