Vitamin A deficiency induces motor impairments and striatal cholinergic dysfunction in rats

Autor: Alessandro Usiello, Elisabetta Tronci, Manolo Carta, Fabio Fadda, Maria Collu, Roberto Stancampiano, Micaela Morelli
Přispěvatelé: Carta, M, Stancampiano, R, Tronci, E, Collu, M, Usiello, Alessandro, Morelli, M, Fadda, F.
Rok vydání: 2006
Předmět:
Zdroj: Neuroscience. 139:1163-1172
ISSN: 0306-4522
DOI: 10.1016/j.neuroscience.2006.01.027
Popis: Vitamin A and its derivatives, retinoids, are involved in the regulation of gene expression by binding two nuclear receptor families, retinoic acid receptors and retinoid X receptors. Retinoid receptors are highly expressed in the striatum, revealing an involvement of this system in the control of movement as demonstrated by previous observations in knockout mice. To further assess the role of retinoids in adult striatal function, the present study investigated the effect of vitamin A deprivation on rat motor activity and coordination, the rate of synthesis and release of dopamine, the functioning of D1 and D2 receptors and their expression in the striatum. Moreover, the content of acetylcholine in the striatum was measured. Results show that 24 weeks of postnatal vitamin A deprivation induced severe locomotor deficits and impaired motor coordination. Vitamin A deprivation rats showed a significant hyperactivity following D1 receptor stimulation by R(+)-6-chloro-7,8-dihydroxy-1-phenyil-2,3,4,5-tetrahydro-1H-3-benzazepine or amphetamine and reduced catalepsy in response to haloperidol treatment. This different response to the above drugs is not due to a change in striatal DA release or synthesis between vitamin A deprivation and control animals. In situ hybridization experiments showed identical level of expression for the D1 and D2 receptor transcripts. On the other hand, the striatal tissue content of acetylcholine was reduced significantly by about 30% starting from the initial manifestation of motor deficits. We suggest that the locomotor impairment could be imputable to the dysfunction in striatal cholinergic interneurons. Our results stress the basic role of vitamin A in the maintenance of basal ganglia motor function in the adult rat brain. Vitamin A and its derivatives, retinoids, are involved in the regulation of gene expression by binding two nuclear receptor families, retinoic acid receptors and retinoid X receptors. Retinoid receptors are highly expressed in the striatum, revealing an involvement of this system in the control of movement as demonstrated by previous observations in knockout mice. To further assess the role of retinoids in adult striatal function, the present study investigated the effect of vitamin A deprivation on rat motor activity and coordination, the rate of synthesis and release of dopamine, the functioning of D1 and D2 receptors and their expression in the striatum. Moreover, the content of acetylcholine in the striatum was measured. Results show that 24 weeks of postnatal vitamin A deprivation induced severe locomotor deficits and impaired motor coordination. Vitamin A deprivation rats showed a significant hyperactivity following D1 receptor stimulation by R(+)-6-chloro-7,8-dihydroxy-1-phenyil-2,3,4,5-tetrahydro-1H-3-benzazepine or amphetamine and reduced catalepsy in response to haloperidol treatment. This different response to the above drugs is not due to a change in striatal DA release or synthesis between vitamin A deprivation and control animals. In situ hybridization experiments showed identical level of expression for the D1 and D2 receptor transcripts. On the other hand, the striatal tissue content of acetylcholine was reduced significantly by about 30% starting from the initial manifestation of motor deficits. We suggest that the locomotor impairment could be imputable to the dysfunction in striatal cholinergic interneurons. Our results stress the basic role of vitamin A in the maintenance of basal ganglia motor function in the adult rat brain. (c) 2006 Published by Elsevier Ltd on behalf of IBRO.
Databáze: OpenAIRE
Externí odkaz: