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Publication : Partial restoration of striatal GABAA receptor balance by functional mesencephalic dopaminergic grafts in mice with hereditary parkinsonism.

First Author  Stasi K Year  1999
Journal  Exp Neurol Volume  157
Issue  2 Pages  259-67
PubMed ID  10364438 Mgi Jnum  J:55410
Mgi Id  MGI:1337920 Doi  10.1006/exnr.1999.7048
Citation  Stasi K, et al. (1999) Partial restoration of striatal GABAA receptor balance by functional mesencephalic dopaminergic grafts in mice with hereditary parkinsonism. Exp Neurol 157(2):259-67
abstractText  Levels of inhibitory amino acid receptors were studied in the weaver (wv/wv) mouse model of dopamine (DA) deficiency after unilateral intrastriatal transplantation of fetal mesencephalic cell suspensions. Graft integration was verified by turning behavior tests and from the topographical levels of the DA transporter, tagged autoradiographically with 3 nM [3H]GBR 12935. The average increase in [3H]GBR 12935 binding in grafted dorsal striatum compared to nongrafted wv/wv striatum was 60% 3 months after grafting. Autoradiography of 8 nM [3H]flunitrazepam and 12 nM [3H]muscimol binding was carried out to visualize the distribution of GABAA receptors in +/+ mice and in recipient weaver mutants. A 17% increase in [3H]flunitrazepam binding and a 20% increase in [3H]muscimol binding was found in the nongrafted dorsal striatum of weaver mutants compared to +/+. The functional mesencephalic grafts had a partial normalizing effect on both [3H]flunitrazepam and [3H]muscimol binding in the dorsal striatum of the weaver recipients. The normalization brought about by the grafts was around 20% for [3H]flunitrazepam binding and more than 40% for [3H]muscimol binding. The results are discussed in the context of the important interaction between the converging glutamatergic corticostriatal and DAergic nigrostriatal pathways in controlling the functional GABAergic output of the basal ganglia in Parkinson's disease and in experimental models of DA deficiency. Copyright 1999 Academic Press.
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