The synaptic impact of the host immune response in a parkinsonian allograft rat model: Influence on graft-derived aberrant behaviors.
Graft-induced dyskinesias (GIDs), side-effects found in clinical grafting trials for Parkinson's disease (PD), may be associated with the withdrawal of immunosuppression. The goal of this study was to determine the role of the immune response in GIDs. We examined levodopa-induced dyskinesias (LIDs), GID-like behaviors, and synaptic ultrastructure in levodopa-treated, grafted, parkinsonian rats with mild (sham), moderate (allografts) or high (allografts plus peripheral spleen cell injections) immune activation. Grafts attenuated amphetamine-induced rotations and LIDs, but two abnormal motor syndromes (tapping stereotypy, litter retrieval/chewing) emerged and increased with escalating immune activation. Immunohistochemical analyses confirmed immune activation and graft survival. Ultrastructural analyses showed increases in tyrosine hydroxylase-positive (TH+) axo-dendritic synapses, TH+ asymmetric specializations, and non-TH+ perforated synapses in grafted, compared to intact, striata. These features were exacerbated in rats with the highest immune activation and correlated statistically with GID-like behaviors, suggesting that immune-mediated aberrant synaptology may contribute to graft-induced aberrant behaviors.
Soderstrom
K E
KE
Department of Neurological Sciences, Rush University, Chicago, IL, USA. katherinesoderstrom@yahoo.com
Meredith
G
G
Freeman
T B
TB
McGuire
S O
SO
Collier
T J
TJ
Sortwell
C E
CE
Wu
Qun
Q
Steece-Collier
K
K
D018663:Adrenergic Agents / Q000633:toxicity; D000661:Amphetamine; D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects; D001522:Behavior, Animal; D004195:Disease Models, Animal; D020820:Dyskinesias / Q000209:etiology* / Q000276:immunology* / Q000473:pathology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007980:Levodopa / Q000009:adverse effects; D008297:Male; D046529:Microscopy, Electron, Transmission; D009043:Motor Activity / Q000187:drug effects; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000188:drug therapy / Q000209:etiology / Q000601:surgery; D051381:Rats; D013569:Synapses / Q000276:immunology* / Q000648:ultrastructure; D016378:Tissue Transplantation / Q000009:adverse effects*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism / Q000648:ultrastructure
D018663:Adrenergic Agents; D000978:Antiparkinson Agents; D000949:Histocompatibility Antigens Class II; D007980:Levodopa; D016627:Oxidopamine; D000661:Amphetamine; D014446:Tyrosine 3-Monooxygenase