RESUMEN
Because epidemiologic and in vitro evidence conflict, the authors studied the association between smoking and Alzheimer disease (AD) in 46 never, 47 former, and 15 active smokers with AD followed to autopsy. Disease parameters were examined by smoking status and amount smoked in bivariate tests and in multivariate models controlling for age, sex, education, and APOE status. Smoking status was not associated with cognitive or neuropathologic measures. However, active smokers were significantly younger at death and higher levels of smoking were associated with shorter disease duration.
Asunto(s)
Enfermedad de Alzheimer/mortalidad , Encéfalo/efectos de los fármacos , Encéfalo/fisiopatología , Fumar/efectos adversos , Fumar/epidemiología , Factores de Edad , Edad de Inicio , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/psicología , Apolipoproteínas E/genética , Encéfalo/patología , Causalidad , Muerte , Progresión de la Enfermedad , Escolaridad , Femenino , Genotipo , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Fenotipo , Estudios Prospectivos , Factores SexualesRESUMEN
In this study, the mechanism of nicotine-induced hippocampal acetylcholine (ACh) release in awake, freely moving rats was examined using in vivo microdialysis. Systemic administration of nicotine (0.4 mg kg(-1), s.c.) increased the levels of ACh in hippocampal dialysates. The nicotine-induced hippocampal ACh release was sensitive to the pretreatment of neuronal nicotinic acetylcholine receptor (nAChR) antagonists mecamylamine (3.0 mg kg(-1), s.c.) and dihydro-beta-erythrodine (DHbetaE; 4.0 mg kg(-1), s.c.) as well as systemic administration of the dopamine (DA) D1 receptor antagonist SCH-23390 (R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-benzaz epine; 0.3 mg kg(-1), s.c.). Local perfusion of mecamylamine (100 microM), DHbetaE (100 microM) or SCH-23390 (10 microM) through microdialysis probe did not increase basal hippocampal ACh release. Hippocampal ACh release elicited by systemic administration of nicotine (0.4 mg kg(-1), s.c.) was antagonized by local perfusion of SCH-23390 (10 microM), but not by MEC (100 microM) or DHbetaE (100 microM). Direct perfusion of nicotine (1 mM, but not 0.1 mM) increased hippocampal ACh levels; however, this effect was relatively insensitive to blockade by co-perfusion of either mecamylamine (100 microM) or SCH-23390 (10 microM). These results suggest that nicotine-induced hippocampal ACh release occurs by two distinct mechanisms: (1) activation of nAChRs outside the hippocampus leading to DA release and subsequent ACh release involving a permissive DA synapse, and (2) direct action of nicotine within the hippocampus leading to ACh release via non-DA-ergic mechanism.