Levels of NGF, p75NGFR and ChAT immunoreactivity in brain of adult and aged microencephalic rats.

Methylazoxymethanol (MAM)-induced microencephalic aged animals with reduced cortical mass and unmodified basal nucleus were used to study the 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 ablation of projecting neurons, we carried out immunohistochemical analysis of ChAT and low affinity NGF receptor (p75NGFR) in the basal nucleus of control and MAM-treated animals. ChAT and p75NGFR immunostaining of basal forebrain cholinergic neurons showed morphological changes in MAM animals, as revealed by cellular atrophy, reduced dendritic arborization and decreased staining intensity. In the cerebral cortex of microencephalic animals, reduced levels of NGF compared to controls were observed at all examined ages. These results suggest that MAM treatment induces long-lasting ablation of cortical NGF-synthesizing cells leading to reduced trophic support to basal forebrain cholinergic neurons, which might be responsible for the cellular atrophy observed in the basal nucleus.

Expression of neuronal acetylcholine nicotinic receptor alpha 4 and beta 2 subunits during postnatal development of the rat brain.

The expression of the alpha 4 and beta 2 subunits of neuronal nicotinic acetylcholine receptors (nAChRs) was studied in developing rat brain using in situ hybridization. The levels of both transcripts were already high at birth in cerebral cortex, medial habenula, CA1/CA3 regions of the hippocampus and several thalamic nuclei. In general, the beta 2 subunit showed a higher density of hybrids than the alpha 4. Beta 2 expression did not change with age in the medial habenula, medial geniculate nucleus or in the hippocampus whereas it decreased in the cortex. The developmental pattern of the hybridization signal for alpha 4 was different according to the brain area considered. The expression of the two transcripts showed a biphasic pattern in some thalamic nuclei: the lowest levels occurring during the first and second postnatal weeks respectively, and the highest levels during the second and fourth postnatal weeks. The ontogenetic profile of the expression of the alpha 4 subunit in the thalamic nuclei coincided with that of [3H]-L-nicotine binding sites. These findings suggest that the two subunits of nAChRs are independently regulated in most of the brain areas examined, and that in some regions, such as the thalamus, the ontogenetic variations reported for the alpha 4 subunit correlate with those observed for the [3H]-L-nicotine binding sites.