LEVELS OF NGF, P75NCFR AND CHAT IMMUNOREACTIVITY IN BRAIN OF ADULT AND AGED MICROENCEPHALIC RATS

Methylazoxymethanol (MAM)-induced microencephalic aged animals with re duced cortical mass and unmodified basal nucleus were used to study th e relationship between cells that produce and cells that utilize NGF. Total cortical ChAT activity of MAM 2, 19 and 27 month old animals was reduced compared to their age-matched controls. To verify whether the reduction of enzyme activity can be ascribed to changes in or ablatio n of projecting neurons, we carried out immunohistochemical analysis o f ChAT and low affinity NGF receptor (p75NGFR) in the basal nucleus of control and MAM-treated animals. ChAT and p75NGFR immunostaining of b asal forebrain cholinergic neurons showed morphological changes in MAM animals, as revealed by cellular atrophy, reduced dendritic arborizat ion and decreased staining intensity. In the cerebral cortex of microe ncephalic animals, reduced levels of NGF compared to controls were obs erved at all examined ages. These results suggest that MAM treatment i nduces long-lasting ablation of cortical NGF-synthesizing cells leadin g to reduced trophic support to basal forebrain cholinergic neurons, w hich might be responsible for the cellular atrophy observed in the bas al nucleus.