title: Fetal striatal transplants restore electrophysiological sensitivity to dopamine in the lesioned striatum of rats with experimental Huntington's disease.
abstract: Dopamine (DA), a major neurotransmitter used in the striatum, is involved in movement disorders such as Parkinson's disease and Huntington's chorea. With the loss of neurons in the striatum of patients with Huntington's disease (HD), there is an associated downregulation of DA receptors, which may alter DA-mediated responses. In the present study, DA-mediated electrophysiological depression was studied in animals with quinolinic acid (QA)-induced experimental HD. QA was directly applied to the right striatum of adult female Sprague-Dawley rats. Animals receiving QA developed ipsilateral rotation after the application of apomorphine. Fetal striatal tissue transplants grafted 1 month after lesioning attenuated apomorphine-induced rotation. Six months after lesioning, the animals were anesthetized with urethane for electrophysiological study. DA, applied directly to neurons by pressure microejection, inhibited spontaneous single-unit activity in the striatal neurons of nonlesioned, lesioned and lesioned/grafted rats. QA lesioning reduced responses to DA in the striatal neurons. The dose of DA required to inhibit striatal neuron activity in the lesioned rats was significantly increased compared to that in the nonlesioned rats. Transplantation of fetal striatal tissue restored the electrophysiological sensitivity to DA in the lesioned striatum. The dose of DA used to suppress striatal neuron activity was reduced after grafting. Immunohistostaining showed survival of gamma-aminobutyric acid neurons at the graft site. Tyrosine hydroxylase-positive terminals were found innervating the striatal grafts. In conclusion, our data demonstrate that fetal striatal transplants restore electrophysiological sensitivity to DA in the lesioned striatum of animals with experimental HD.
authors.affiliation: Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Guann-Juh
authors.initials: GJ
authors.lastname: Chen
authors.forename: Chern-Hueih
authors.initials: CH
authors.lastname: Jeng
authors.forename: Shinn-Zong
authors.initials: SZ
authors.lastname: Lin
authors.forename: Shin-Hin
authors.initials: SH
authors.lastname: Tsai
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.forename: Yung-Hsiao
authors.initials: YH
authors.lastname: Chiang
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D016380:Brain Tissue Transplantation; D003342:Corpus Striatum / Q000187:drug effects* / Q000196:embryology / Q000502:physiology / Q000637:transplantation*; D004195:Disease Models, Animal; D004298:Dopamine / Q000494:pharmacology*; D004594:Electrophysiology; D005260:Female; D016332:Fetal Tissue Transplantation; D006085:Graft Survival; D006801:Humans; D006816:Huntington Disease / Q000503:physiopathology* / Q000601:surgery; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D017378:Quinolinic Acid / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000378:metabolism; D012399:Rotation; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D011954:Receptors, Dopamine; D005680:gamma-Aminobutyric Acid; D014446:Tyrosine 3-Monooxygenase; D017378:Quinolinic Acid; D001058:Apomorphine; D004298:Dopamine