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Effet protecteur des greffes intrastriatales dans un modèle expérimental de maladie de Huntington. Corrélation comportementale et morphologique [Protective effect of intrastriatal grafts in an experimental model of Huntington's disease. Behavioral and morphological correlation].
Publication types: English Abstract ; Journal Article ; Research Support, Non-U.S. Gov't ; Review
Publication Status: ppublish
Publication Status: ppublish
The intrastriatal injection of the excitotoxin quinolinic acid (Q.A.) in rats produces neuroanatomical and neurochemical changes mimicking those appearing in the striatum in Huntington's disease (H.D.). Although its cause is unknown, it has been hypothesized that the neurodegenerative changes seen in H.D. may result from the action of an endogenous toxin. Therefore, the development of new strategies for limiting or preventing Q.A.-or other neurotoxic-induced degeneration may be of therapeutic interest for neurodegenerative disorders. Accordingly, we tested the ability of various tissue transplants to protect the rat striatum against a subsequent Q.A. insult. Using a "unilateral model", i.e. unilateral intrastriatal grafts followed by an ipsilateral intrastriatal injection of Q.A., we were able to quantify a behavioral protective effect of the grafts in recording the apomorphine-induced rotational behavior that normally appears after the striatal Q.A.-induced lesion. Our results show that one of the tested tissue, fetal striatum, protects the recipients against the lesioned-induced rotational behavior that appeared in non-grafted lesioned animals. The other grafted tissues (adrenal medulla, peripheral nerve, adipose tissue) seemed to provide a less dramatic protection than fetal striatum; however, this difference did not reach significance. Quantification of the striatal neuronal loss showed that the behavioral protection is significantly correlated with a better neuronal survival in the grafted animals. These results suggest that intracerebral grafts can protect the host brain against a toxin-induced damage, like the one resulting from Q.A. intrastriatal injection. Though fetal striatal grafts seem to exert an optimal protection, this protective effect may at least partially result from a host-mediated response to the transplantation procedure. The mechanism underlying this protective effect is unclear, but the present data suggest that it might be related to a transplantation-induced astroglial reaction resulting in an increased neuronotrophic activity that could protect against the toxic effect of Q.A. The results of this study also support the concept that the effect of transplantations could occur through processes other than a direct restoration of deficient transmitters or a reconstruction of damaged pathways. Further characterization of the factors implicated in the present paradigm might conceivably open avenues for possible therapeutic preventive interventions in neurodegenerative disorders.
Animals, Behavior, Animal, Corpus Striatum/pathology, Corpus Striatum/transplantation, Disease Models, Animal, Female, Huntington Disease/surgery, Pregnancy, Quinolinic Acids/administration & dosage, Rats
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