Brain implantations of engineered GABA-releasing cells suppress tremor in an animal model of Parkinsonism.
Traditional approaches in the treatment of Parkinson's disease have typically been directed at restoring dopaminergic tone in the neostriatum of the basal ganglia. Nevertheless, the vast majority of neostriatal efferent projections use GABA as their neurotransmitter. Substantia nigra pars reticulata (SNr) is a major basal ganglia output area that is a target of these GABAergic projections, and research from animal models has indicated that stimulation of GABA receptors in SNr can produce motor effects consistent with an antiparkinsonian action. In the present study, implantation of engineered GABA-releasing cells into SNr reduced tremulous movements in an animal model of parkinsonian tremor. These results suggest that implantation of GABA cells into SNr, or possibly into other basal ganglia structures, could provide an alternative transplantation strategy for the treatment of Parkinsonism.
Carlson
B B
BB
College of Liberal Arts and Sciences, Department of Psychology, Division of Behavioral Neuroscience, University of Connecticut, 406 Babbidge Road, U-20, Storrs, CT 06269-1020, USA.
Behrstock
S
S
Tobin
A J
AJ
Salamone
J D
JD
D000818:Animals; D016380:Brain Tissue Transplantation / Q000379:methods*; D002460:Cell Line / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D004195:Disease Models, Animal; D005818:Genetic Engineering / Q000379:methods; D005968:Glutamate Decarboxylase / Q000096:biosynthesis / Q000235:genetics; D006085:Graft Survival / Q000235:genetics; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D009433:Neural Inhibition / Q000235:genetics; D020734:Parkinsonian Disorders / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D016896:Treatment Outcome; D014202:Tremor / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*
D007527:Isoenzymes; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2