RESUMO
The cholinergic system is involved in cognition and several forms of dementia, including Alzheimer's disease, and nicotine administration has been shown to improve cognitive performance in both humans and rodents. While experiments with humans have shown that nicotine improves the ability to handle an increasing working memory load, little work has been done in animal models evaluating nicotine effects on performance as working memory load increases. In this report, we demonstrate that in aged rats nicotine improved the ability to handle an increasing working memory load as well as enhanced performance on the reference memory component of the water radial arm maze task. The dose required to exert these effects (0.3mg/kg/day) was much lower than doses shown to be effective in young rats and appears to be a lower maintenance dose than is seen in light to moderate smokers. In addition, our study reports a nicotine-induced reduction in nerve growth factor (NGF) protein levels in the hippocampus of the aged rat. The effects of nicotine on hippocampal NGF levels are discussed as a potential mechanism of nicotine-induced improvements in working and reference memory.
Assuntos
Envelhecimento/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Memória/efeitos dos fármacos , Fator de Crescimento Neural/metabolismo , Nicotina/administração & dosagem , Agonistas Nicotínicos/administração & dosagem , Análise de Variância , Animais , Comportamento Animal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Cotinina/sangue , Relação Dose-Resposta a Droga , Esquema de Medicação , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/classificação , Ratos , Espectrofotometria/métodosRESUMO
The data in this report describe the discovery and characterization of a previously unidentified alternatively processed RNA for the neuronal nicotinic receptor alpha7 subunit. The unique transcript contains an extra exon that arises from alternative splicing of intron nine of the alpha7 subunit RNA. The alpha7 subunit protein resulting from this alternatively processed RNA is truncated shortly after transmembrane domain three. The variant protein also has a predicted amino acid substitution in the large N-terminal domain as a consequence of a non-templated nucleotide substitution present in the variant alpha7 subunit RNA. The mechanism responsible for the nucleotide substitution is not known. Initial characterization of the variant alpha7 subunit suggests that it is expressed in mouse brain in a pattern similar to the standard alpha7 subunit although at reduced levels. The variant alpha7 subunit was also found to act as a dominant-negative effecter of normal alpha7 subunit function.
