Assessment of recovery in the hemiparkinson rat: drug-induced rotation is inadequate.
Physiol Behav
; 84(4): 525-35, 2005 Mar 31.
Article
em En
| 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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transtornos da Percepção
/
Transplante de Tecido Encefálico
/
Recuperação de Função Fisiológica
/
Transtornos Parkinsonianos
/
Atividade Motora
/
Destreza Motora
Limite:
Animals
Idioma:
En
Revista:
Physiol Behav
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Estados Unidos