Training specificity, graft development and graft-mediated functional recovery in a rodent model of Huntington's disease.
Neuronal function and morphology are affected by the environment and the behavioral experience. Here we report on the effects of differential training protocols on the development and the functional recovery mediated by intrastriatal striatal grafts. Rats were trained exclusively on the left or the right paw to perform on the skilled staircase task before being lesioned unilaterally in the dorsal striatum with quinolinic acid. E15 whole ganglionic eminence suspension grafts were implanted into the lesioned striatum. Subsequent testing probed unilateral performance of the affected contralateral paw, as well as bilateral performance. The grafted animals were initially as impaired as the lesioned, but partially recovered their performance with additional training. Grafted animals with appropriate previous experience initially performed better on the staircase test, but the advantage was transient. Furthermore, the grafted animals performed better with their affected paw under forced choice than under conditions when both paws were simultaneously probed. Improvements of the grafted animals were also observed on tests of forelimb akinesia and asymmetry. Morphological data suggest that the training conditions influenced the development specifically of striatal-like, but not of non-striatal like, neurones within the grafts. The grafts were smaller containing less striatal-like neurones in animals that were trained on the contralateral side prior to lesioning and grafting. The results support the hypothesis that unilateral training sensitizes the striatum that subserves the motor learning, leading to exacerbated excitotoxic lesions and to an environment less conducive for graft development.
Döbrössy
M D
MD
Brain Repair Group, School of Biosciences, Cardiff University, Museum Avenue Box 911, Cardiff CF10 3US, UK. dobrossymd@cf.ac.uk
Dunnett
S B
SB
D000818:Animals; D001522:Behavior, Animal; D016380:Brain Tissue Transplantation / Q000502:physiology*; D002452:Cell Count / Q000379:methods; D003342:Corpus Striatum / Q000473:pathology / Q000637:transplantation*; D004195:Disease Models, Animal; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D004622:Embryo, Mammalian; D007839:Functional Laterality / Q000502:physiology; D006085:Graft Survival; D006816:Huntington Disease / Q000503:physiopathology / Q000628:therapy*; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000379:methods*; D011597:Psychomotor Performance / Q000502:physiology; D017378:Quinolinic Acid / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D014446:Tyrosine 3-Monooxygenase; D010751:Phosphopyruvate Hydratase; D017378:Quinolinic Acid