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

Interest in the basal forebrain cholinergic system has greatly increased since 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 neurones has been produced by several neurotoxic insults in order to obtain a model reproducing the behavioural impairment related to the cholinergic deficits. The experiments reported in this review demonstrate that excitotoxic amino acids, beta-amyloid and lipopolysaccharide, injected directly in the nucleus 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 investigating drugs able to ameliorate the cholinergic functions. Local injections of amyloid peptides in the rat nucleus basalis produced cholinergic hypofunction and some behavioural impairment. Finally, an intense glia reaction with a limited cholinergic hypofunction and no behavioural impairment was induced by a 4-week infusion of lipopolysaccharide in the nucleus basalis. In conclusion, all three models, in spite of their limitations, offer useful tools for the study of the pathogenetic mechanisms of Alzheimer's disease and for investigating potentially useful drugs.