- 作者: Guann-Juh Chen a, Churn-Hueih Jeng b, Shinn-Zong Lin a, Shin-Han Tsai c, Yun Wang d, Yung-Hsiao Chiang a
- 作者服務機構: a Department of Neurological Surgery, Tri-Service General Hospital, b Department of Pharmacology, National Defense Medical Center, c Institute of Injury Prevention and Control, Taipei Medical University Taipei, Taiwan, ROC, d National Institute on DrugAbuse, Baltimore, Md., USA
- 中文摘要: --
- 英文摘要: Dopamine (DA), a major neurotransmitter used in thestriatum, is involved in movement disorders such as Par-kinson's disease and Huntington's chorea. With the lossof neurons in the striatum of patients with Huntington'sdisease (HD), there is an associated downregulation ofDA receptors, which may alter DA-mediated responses.In the present study, DA-mediated electrophysiologicaldepression was studied in animals with quinolinic acid(QA)-induced experimental HD. QA was directly appliedto the right striatum of adult female Sprague-Dawleyrats. Animals receiving QA developed ipsilateral rotationafter the application of apomorphine. Fetal striatal tissuetransplants grafted 1 month after lesioning attenuatedapomorphine-induced rotation. Six months after lesion-ing, the animals were anesthetized with urethane forelectrophysiological study. DA, applied directly to neu-rons by pressure microejection, inhibited spontaneoussingle-unit activity in the striatalneurons of nonlesioned,lesioned and lesioned/grafted rats. QA lesioning reducedresponses to DA in the striatal neurons. The dose of DArequired to inhibit striatal neuron activity in the lesionedrats was significantly increased compared to that in thenonlesioned rats. Transplantation of fetal striatal tissuerestored the electrophysiological sensitivity to DA in thelesioned striatum. The dose of DA used to suppress stria-tal neuron activity was reduced after grafting. Immuno-histostaining showed survival of -aminobutyric acidneurons at the graft site. Tyrosine hydroxylase-positiveterminals were found innervating the striatal grafts. Inconclusion, our data demonstrate that fetal striatal trans-plants restore electrophysiological sensitivity to DA inthe lesioned striatum of animals with experimental HD.
- 中文關鍵字: --
- 英文關鍵字: Huntington's disease, Neural transplantation, Dopamine, Regeneration, Electrophysiology, Striatum