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Physiol Behav ; 84(4): 525-35, 2005 Mar 31.
Article in English | MEDLINE | ID: mdl-15811387

ABSTRACT

Recovery from apomorphine-induced rotational behavior was compared to sensorimotor and motor function in hemiparkinsonian rats receiving intrastriatal grafts of astrocytes expressing recombinant tyrosine hydroxylase (TH) or control beta-galactosidase (beta-gal). Rats received unilateral intranigral infusions of 6-hydroxydopamine (6-OHDA). Animals with large lesions, as determined by apomorphine-induced rotation, received grafts of astrocytes into the denervated striatum. Behavioral recovery was assessed on days 14-16 post-transplantation using apomorphine-induced rotation, somatosensory neglect, and reaching for pellets using the Montoya staircase method. Rats that received transplants of TH-transfected astrocytes showed a 34% decrease in rotational behavior, but no consistent recovery of somatosensory neglect or skilled reaching. Post-mortem histological analyses revealed survival of grafted astrocytes in host striatum and expression of TH at 17 days post-transplantation. We suggest that TH-expressing astrocytes may reverse post-synaptic dopamine (DA) receptor supersensitivity; however, sensorimotor and motor abilities are not restored due to a failure by TH-expressing astrocytes to reestablish dopaminergic circuitry. The present results demonstrate the need to utilize a variety of sensory and motor behavioral tests that cohesively provide greater interpretability than a single behavioral measure used in isolation, such as drug-induced rotational behavior, to assess the efficacy of experimental gene therapies.


Subject(s)
Brain Tissue Transplantation/physiology , Motor Activity/physiology , Motor Skills/physiology , Parkinsonian Disorders/physiopathology , Parkinsonian Disorders/surgery , Perceptual Disorders/surgery , Recovery of Function/physiology , Animals , Apomorphine , Astrocytes/metabolism , Astrocytes/transplantation , Behavioral Research/methods , Corpus Striatum/cytology , Corpus Striatum/metabolism , Corpus Striatum/surgery , Denervation , Dopamine/metabolism , Male , Motor Activity/drug effects , Oxidopamine , Parkinsonian Disorders/chemically induced , Perceptual Disorders/therapy , Rats , Rats, Inbred F344 , Rotation , Stereotyped Behavior , Substantia Nigra/drug effects , Treatment Outcome
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