Striatal transplantation in a rodent model of multiple system atrophy: effects on L-Dopa response.
Progressive degeneration of striatal projection neurons is thought to account for the loss of L-Dopa response observed in the majority of patients with the parkinsonian variant of multiple system atrophy (MSA-P). Here we have investigated the effects of E14 embryonic striatal allografts on dopaminergic responsiveness in the unilateral double-lesion rat model of MSA-P by using tests of complex motor behavior. Both sham and graft animals showed an increase in apomorphine-induced rotations as well as an improvement in cylinder test performance following surgical intervention. In contrast, L-Dopa responsiveness of stepping behavior was improved only in grafted animals. The restoration of apomorphine-induced rotation correlated with the P-zone volume of grafts. Our findings indicate that transplantation of embryonic striatal grafts might, at least to some extent, restore responsiveness to L-Dopa in tasks of complex motor behavior. Therefore, striatal transplantation should be further defined preclinically as a possible therapeutic option for patients with MSA-P and a failing L-Dopa response.
Köllensperger
Martin
M
Section for Clinical Neurobiology, Innsbruck Medical University, Innsbruck, Austria.
Stefanova
Nadia
N
Pallua
Anton
A
Puschban
Zoe
Z
Dechant
Georg
G
Hainzer
Monika
M
Reindl
Markus
M
Poewe
Werner
W
Nikkhah
Guido
G
Wenning
Gregor K
GK
D000704:Analysis of Variance; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001921:Brain / Q000473:pathology; D003342:Corpus Striatum / Q000196:embryology / Q000637:transplantation*; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000627:therapeutic use*; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D019578:Multiple System Atrophy / Q000188:drug therapy / Q000503:physiopathology / Q000628:therapy*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014184:Transplantation, Homologous
D015259:Dopamine Agents; D007980:Levodopa; D001058:Apomorphine