Nigral injection of antisense oligonucleotides to synaptotagmin I using HVJ-liposome vectors causes disruption of dopamine release in the striatum and impaired skill learning.
Brain Res
; 1095(1): 178-89, 2006 Jun 20.
Article
em En
| MEDLINE
| ID: mdl-16729982
ABSTRACT
To produce an animal model of a dopa-responsive motor disorder with depletion of dopamine (DA) release in the striatum by dysfunction of the transmitter release machinery of the nigrostriatal DA system, we performed an intra-nigral injection of an HVJ-liposome gene transfer vector containing antisense oligodeoxynucleotides (ODNs) against synaptotagmin I (SytI), a key regulator of Ca(2+)-dependent exocytosis and endocytosis in adult rats. A unilateral intra-nigral injection of HVJ-liposome vectors containing antisense ODNs against SytI (syt-AS) caused a moderate disruption of methamphetamine-induced release of DA in the treated side of the striatum, while the syt-AS treatment did not affect physiological release of DA in the treated striatum. A bilateral intra-nigral injection of HVJ-liposome vectors containing syt-AS induced an impairment of the striatal DA-mediated acquisition of skilled behavior in a rotarod task without any deficits in general motor functions, such as spontaneous locomotor activity, motor adjusting steps, equilibrium function, or muscle strength. These findings suggest that an intra-nigral treatment with HVJ-liposome vectors containing syt-AS may cause a long-lasting nigral knockdown of SytI which, in turn, leads to a moderate dysfunction of the DA release machinery in the terminals of the nigrostriatal DA system and a subsequent mild depletion of DA release in the striatum.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Substância Negra
/
Oligonucleotídeos Antissenso
/
Técnicas de Transferência de Genes
/
Transtornos das Habilidades Motoras
/
Corpo Estriado
/
Atividade Motora
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Brain Res
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Japão