Dopaminergic responses to striatal damage.
The improvements obtained by grafting dopamine-rich tissues into the striatum of patients with Parkinson's disease are generally attributed to production and release of dopamine by the graft. However, it is becoming increasingly clear that grafting also stimulates the host dopaminergic system. We provide evidence in a mouse model of striatal damage that surgical cavitation induces a concerted response from the dopaminergic system with proliferation of striatal presynaptic dopamine uptake sites, increased tyrosine hydroxylase activity, increased concentrations of dopamine, dihydroxyphenylacetic acid and homovanillic acid. The response increases with time and ultimately includes contralateral stimulation of striatal tyrosine hydroxylase activity and elevation of dihydroxyphenylacetic acid and homovanillic acid concentrations. The time course and extent of the host dopaminergic response suggests that it may make a significant contribution to observed clinical improvements after intrastriatal transplantation in human parkinsonism.
Howells
D W
DW
Department of Neurology, University of Melbourne, Austin, Australia.
Liberatore
G T
GT
Wong
J Y
JY
Donnan
G A
GA
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D016380:Brain Tissue Transplantation; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology*; D004295:Dihydroxyphenylalanine / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D007839:Functional Laterality; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D008297:Male; D008454:Mazindol / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010300:Parkinson Disease / Q000473:pathology / Q000601:surgery; D012016:Reference Values; D013569:Synapses / Q000378:metabolism; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D015102:3,4-Dihydroxyphenylacetic Acid; D004295:Dihydroxyphenylalanine; D008454:Mazindol; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D006719:Homovanillic Acid