Toxicidad neuronal de la interleucina-2 recombinante humana en ratas: validación morfoconductual / Neuronal toxicity of human recombinant interleukin 2 in rats: morphoconductual validation

Introducción y objetivo. La afectación de memoria que se observa en el envejecimiento es una manifestación de la disminución de las funciones cognitivas con la edad, la cual está estrechamente asociada a cambios neuropatológicos y bioquímicos en áreas colinérgicas del sistema nervioso central (SNC). Las citoquinas, descritas por primera vez como moléculas inmunoreguladoras, están también implicadas en reacciones defensivas del cerebro. Estudios relacionados con la acción de la IL-2 sobre el SNC le atribuyen un efecto bloqueador sobre la secreción de acetilcolina a nivel hipocampal. Material y métodos. Hemos desarrollado un estudio dirigido a caracterizar los efectos neurotóxicos centrales de esta citoquina mediante la infusión crónica intraperitoneal de IL-2 recombinante humana (IL-2rh) en ratas jóvenes y viejas de la línea Sprague Dawley. Resultados y conclusiones. Los resultados obtenidos, aunque parciales, no parecen referir el posible efecto in vivo de la IL-2 sobre la función colinérgica central, pero si son consistentes con la implicación probable de esta citoquina en el deterioro cognitivo senescente y, de manera particular, en el deterioro de la memoria espacial asociada a la edad y/o en el curso de trastornos neurodegenerativos relacionados

Effects of chronic infusion of nerve growth factor (NGF) in rats with nucleus basalis magnocellularis lesion

We attempted to evaluate the effects of bilaeral injection of ibotenic acid (IA) into the nucleus basalis magnocelluraris (rbm) of rats as well as the potential recovery mediated by the infusion of nerve growth factor (NGF). The lesion caused and impairment of learning and memory processes. Also, a severe depletion of choline acetyl transferase activity was detected in cortical areas. After the NGF administration, a significant reversion of these functional changes was observed. Thus, IA-lesioned rats might serve as a model for the evaluation of neurotrophic factors actions on basal forebrain damaged neurons

Effects of chronic infusion of nerve growth factor (NGF) in AF64A-lesioned rats

We report here the behavioral and biochemical recovery induced by the nerve growth factor (NGF) administration in AF64A-treated rats. Retention in the passive avoidance test was affected by lesion but it was significantly improved after the NGF treatment. Similar resultas were observed in the performance during the Morris water maze (MWM) task. Remarkable losses in the ChAT activity were detected in some brain regions from lesioned rats. The NGF-induced alleviation of choline acetyl transferase (ChAT) activity losses and cognitive functions suggest a trophic and protective action on the remaining cholinergic neurons after the lesion. Thus NGF therapy could be considered as a possibility mainly in the early course of Alzheimer disease

Neurorestorative techniques as experimental approach to Alzheimer disease treatment

Laboratory animals have been used to reproduce some structural changes and/or memory impairment observed in Alzheimer disease by means of specific lesions or using old animals (Kordower and Gash, 1986). Different sources and places for the neural graft have been reported showing the graft's ability to attain an adequate and specific innervation of the target as well as the behavioral recovery (Dunnett, 1991; Gage and Chen, 1992). Similar experimental procedures have been used to evaluate effects of exogenous nerve growth factor (NGF) infusion, whose influence on central cholinergic neurons is well documented (Gage et al. 1991; Pepeu et al., 1993)