Reduced density of neuropeptide Y neurons in the somatosensory cortex of old male and female rats: Relation to cholinergic depletion and recovery after nerve growth factor treatment

Synthesis of neuropeptide Y in the neocortex and activity of the basalocortical cholinergic system are both reduced in the aging brain. We hypothesized that, by stimulating the activity of the basal forebrain cholinergic neurons, nerve growth factor might also be capable of restoring the synthesis of neuropeptide Y in cortical neurons. Old male and female rats were intraventricularly infused with nerve growth factor for 14 days and their brains were analyzed in order to quantify the densities of neuropeptide Y-immunoreactive neurons and of fiber varicosities stained for vesicular acetylcholine transporter protein in layers III/III, V and VI of the primary somatosensory barrel-field cortex. The areal densities of neuropeptide Y neurons and of vesicular acetylcholine transporter protein varicosities in all cortical laminae were found to be dramatically decreased in old rats when compared with young rats. However, infusions of nerve growth factor, known to exert a powerful trophic effect upon cortically projecting cholinergic neurons, have led to considerable recovery of vesicular acetylcholine transporter protein-positive terminal fields, which was paralleled by complete restoration of function in neuropeptide Y-producing neurons. With respect to the gender differences, although the density of cortical neuropeptide Y neurons was found to be significantly higher in young females than in young males and the opposite was true for vesicular acetylcholine transporter protein-positive varicosities, the general pattern of age- and treatment-related changes in these neurochernical markers was similar in both sexes. Overall, the age- and treatment-related variations in the density of cortical neuropeptide Y cells were found to correlate with those observed in the density of vesicular acetylcholine transporter protein varicosities. These results lend support to the idea that there is a causal relationship between age-related changes in cortical cholinergic and neuropeptide Y-ergic neurotransmitter systems. (c) 2005 Published by Elsevier Ltd on behalf of IBRO.