RESUMEN
BACKGROUND AND PURPOSE: Previous evidence from MRI and acetylcholinesterase histochemistry suggests cholinergic fibers are affected in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). METHODS: As a measure of cholinergic function, we assessed choline acetyltransferase (ChAT) activities in the frontal and temporal neocortices and the immunocytochemical distribution of ChAT and p75 neurotrophin receptor (P75(NTR)) by in vitro imaging in the nucleus basalis of Meynert of CADASIL subjects. RESULTS: ChAT activities were significantly reduced by 60% to 70% in frontal and temporal cortices of CADASIL cases, as were ChAT and P75(NTR) immunoreactivities in the nucleus basalis. CONCLUSIONS: Our findings suggest cholinergic neuronal impairment in CADASIL and implicate cholinomimetic therapy for subcortical vascular dementias.
Asunto(s)
Núcleo Basal de Meynert/metabolismo , CADASIL/metabolismo , Colina O-Acetiltransferasa/metabolismo , Fibras Colinérgicas/metabolismo , Lóbulo Frontal/metabolismo , Vías Nerviosas/metabolismo , Lóbulo Temporal/metabolismo , Anciano , Anciano de 80 o más Años , Núcleo Basal de Meynert/patología , CADASIL/patología , Arterias Cerebrales/metabolismo , Arterias Cerebrales/patología , Fibras Colinérgicas/patología , Regulación hacia Abajo/fisiología , Femenino , Lóbulo Frontal/patología , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Vías Nerviosas/patología , Receptor de Factor de Crecimiento Nervioso/metabolismo , Lóbulo Temporal/patologíaRESUMEN
Ten days treatment with nicotine reduced insoluble amyloid A beta 1-40 and Alpha beta 1-42 peptides by 80% in the cortex of 9-month-old APPsw mice, which is more than that observed in 14.5-month-old mice following nicotine treatment for 5.5 months. A reduction in A beta associated with cerebral vessels was observed in addition to that deposited as parenchymal plaques after 5.5 months treatment. The diminution in A beta peptides observed was not accompanied by changes in brain alpha, beta or gamma secretase-like activities, NGF or BDNF protein expression measured in brain homogenates. A significant increase in sAPP was observed after nicotine treatment of SH-SY5Yneuroblastoma cells that could be blocked by the nicotinic antagonist mecamylamine. Attenuation of elevated [(125)I]-alpha bungarotoxin binding (alpha 7) in APPsw mice was observed after 5.5 months nicotine treatment. Both these observations suggest that the reduction in insoluble A beta by nicotine might be in part mediated via the alpha 7 nicotinic receptor. Further studies are required to identify potential mechanisms of the nicotine's amyloid-reducing effect.