Amino acid transporter Asc-1 (SLC7A10) expression is altered in basal ganglia in experimental Parkinsonism and L-dopa-induced dyskinesia model mice

• Material Type: 博士論文
• Title: Amino acid transporter Asc-1 (SLC7A10) expression is altered in basal ganglia in experimental Parkinsonism and L-dopa-induced dyskinesia model mice
• Author/Editor: Nakahara, Kazuki; Okuda, Hiroaki; Isonishi, Ayami; Kawabe, Yoshie; Tanaka, Tatsuhide; Tatsumi, Kouko; Wanaka, Akio
• Author Heading: Nakahara, Kazuki; Okuda, Hiroaki; Isonishi, Ayami; Kawabe, Yoshie; Tanaka, Tatsuhide; Tatsumi, Kouko; Wanaka, Akio
• Publication, Distribution, etc.: Elsevier B.V.
• Publication Date: 2023-01; 127
• Publication Date (W3CDTF): 2023-01
• Alternative Title: 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
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2024-03-14
• Date Granted (W3CDTF): 2024-03-14
• Dissertation Number: 甲第901号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: Amino acid transporter Asc-1 (SLC7A10); Basal ganglia; 6-hydroxydopamine (6-OHDA); Parkinson’s disease (PD); L-dopa-induced dyskinesia (LID); Laser microdissection
• Target Audience: 一般
• Note (General): type:Thesis; 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.; 権利情報：© 2022 Elsevier B.V. All rights reserved.; identifier:Journal of Chemical Neuroanatomy. 2023 Jan, vol.127, article no.102191; identifier:0891-0618; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/4352; identifier:Journal of Chemical Neuroanatomy, 127: 102191
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• Date Accepted (W3CDTF): 2024-06-07T22:11:46+09:00
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• Periodical Title (URI): http://hdl.handle.net/10564/4352
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