Neuropeptide Y and somatostatin in the neocortex of young and aging rats: Response to nucleus basalis lesions

Abstract

Lesions of the nucleus basalis of Meynert (NBM) have been used to mimic, in part, cholinergic deficits occurring in age-related neurodegenerative disorders, i.e., Alzheimer's disease. In our study, the effect of a persistent cholinergic denervation of the frontoparietal cortex on neuropeptide Y (NPY) and somatostatin (SOM) was examined in young adult (3 months old) and aging (> 18 months old) rats, 1, 3 and 6 months after bilateral stereotaxic NBM lesions with quisqualic acid. In aging, non-lesioned rats a significant decrease in radioimmunologically and immunohistochemically detectable NPY and SOM was found with no further changes after lesions. Morphological markers for these peptidergic populations (cell size and number, NADPH-diaphorase histochemistry, electron microscopy) demonstrated no signs of alterations in both age groups after lesion. Densitometric analysis of peptide fibre networks displayed a heterogeneous response with a significant rarefication in young rats 1 month after the lesion, followed by restoration and a tendency towards increase 6 months post lesioning in individual animals. These findings were confirmed by radioimmunological measurements. Examination of synaptic and cytoskeletal markers, i.e., synaptophysin, GAP-43, MAP-2, Tau-1 and amyloid precursor protein, did not reveal any signs for neuronal reorganization or sprouting. These data are discussed in the context of plasticity and pathology in age-related neurodegenerative disorders with cholinergic impairment.