Morphological, biochemical and behavioural changes induced by neurotoxic and inflammatory insults to the nucleus basalis

Interest in the basal forebrain cholinergic system has greatly increased si nce neuropathological studies in humans provided evidence that this system is severely affected in Alzheimer's disease and other dementing disorders. In laboratory animals, disruption of the nucleus basalis cholinergic neuron es has been produced by several neurotoxic insults in order to obtain a mod el reproducing the behavioural impairment related to the cholinergic defici ts. The experiments reported in this review demonstrate that excitotoxic amino acids, beta-amyloid and lipopolysaccharide, injected directly in the nucleu s basalis are toxic to the cholinergic neurones in the rat. The excitotoxin lesions of the nucleus basalis, although not selective, are a useful tool for producing experimental animals with cholinergic hypofunction and for in vestigating drugs able to ameliorate the cholinergic functions. Local injec tions of amyloid peptides in the rat nucleus basalis produced cholinergic h ypofunction and some behavioural impairment. Finally, an intense,alia react ion with a limited cholinergic hypofunction and no behavioural impairment w as induced by a 4-week infusion of lipopolysaccharide in the nucleus basali s. In conclusion, all three models, in spite of their limitations, offer usefu l tools for the study of the pathogenetic mechanisms of Alzheimer's disease and for investigating potentially useful drugs. (C) 1999 ISDN. Published b y Elsevier Science Ltd. All rights reserved.