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    Please use this identifier to cite or link to this item: https://nccur.lib.nccu.edu.tw/handle/140.119/157161


    Title: 以瑞特氏症模式小鼠研究運動障礙之療癒—聚焦紋狀體神經迴路
    In Search of Interventions to Ameliorate Motor Deficits in Mouse Model of Rett Syndrome: Focusing on the Neural Circuit of the Striatum
    Authors: 廖文霖
    Contributors: 神科所
    Keywords: 瑞特氏症;紋狀體;基底核;運動控制;光遺傳學;條件缺失小鼠
    Rett syndrome;Striatum;Basal ganglia;Motor control;Optogenetics;Conditional knockout mouse
    Date: 2021-11
    Issue Date: 2025-05-29 11:56:53 (UTC+8)
    Abstract: 瑞特氏症 (Rett Syndrome, RTT) 是由第二型甲基CpG結合蛋白 (methyl-CpG binding protein 2, MeCP2) 之基因突變所導致的一種神經發育疾病，患者多出現明顯的運動障礙。許多研究致力於探討治療RTT的方法，但至今仍未發展出可以有效且完全改善RTT 運動障礙的療法。我們先前的研究發現，前端紋狀體很可能是RTT運動障礙之病灶所在，因此推測若調整此腦區的神經活性有可能改善RTT模式小鼠的運動功能。在光遺傳學的先導實驗中，我們已經初步發現抑制前端紋狀體中GABA神經元的活性可以明顯增加小鼠在在開放空間中的運動活力。因此，於本計劃中我們將嘗試以光刺激選擇性地抑制前端紋狀體的GABA神經元 (Aim 1)，或抑制其投射區「黑質網狀區」之GABA神經元活性(Aim 2) 來觀察其是否可以有效減輕RTT模式小鼠的運動障礙。另外，我們也嘗試操弄前端紋狀體中兩條不同的傳出路徑 -「直接路徑」及「間接路徑」- 的神經活性，來測試是否可以改善Mecp2缺失小鼠的運動障礙(Aim 3)。本研究之成果將不只讓我們更加了解運動控制的神經迴路，也可望提供更精確有效的治療方法來減輕RTT的運動障礙。
    Rett Syndrome (RTT), caused by mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene, is an developmental neurological disorder with striking psychomotor deficits. Numerous therapeutic strategies have been tested in mouse model of RTT, but none of them shows complete restoration in motor dysfunction to date. Our previous findings demonstrate that the rostral striatum (ST-r) is the brain region necessary and sufficient to affect locomotion in RTT-like mice, raising the possibility that manipulating the neuronal activity in the ST-r may restore motor deficits in RTT. Supporting of this, our preliminary study shows that optogenetically inactivation of the GABAergic neurons in the ST-r enhances locomotor activity in normal mice. Therefore, in this proposal, we will further explore whether hypokinesia of RTT-like mice can be restored by selectively inactivating the GABAergic neurons in the ST-r (Aim 1) or its projection area, the substentia nigra pars reticularta (Aim 2) by optogenetic approach. We also plan to investigate the roles of the striatal efferents, the direct or indirect pathways, from the ST-r in locomotor modulation in Mecp2 deficiency mice (Aim 3). Our findings will give us an insight into the neuronal and circuit control of psychomotor function and provide a cellular basis for developing effective interventions to ameliorate psychomotor deficits in RTT.
    Relation: 科技部, MOST107-2320-B004-001-MY3, 107.08-110.07
    Data Type: report
    Appears in Collections:[神經科學研究所] 國科會研究計畫

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