Old-onset caloric restriction effects on neuropeptide Y- and somatostatin-containing neurons and on cholinergic varicosities in the rat hippocampal formation.

Caloric restriction is able to delay age-related neurodegenerative diseases and cognitive impairment. In this study, we analyzed the effects of old-onset caloric restriction that started at 18 months of age, in the number of neuropeptide Y (NPY)- and somatostatin (SS)-containing neurons of the hippocampal formation. Knowing that these neuropeptidergic systems seem to be dependent of the cholinergic system, we also analyzed the number of cholinergic varicosities. Animals with 6 months of age (adult controls) and with 18 months of age were used. The animals aged 18 months were randomly assigned to controls or to caloric-restricted groups. Adult and old control rats were maintained in the ad libitum regimen during 6 months. Caloric-restricted rats were fed, during 6 months, with 60 % of the amount of food consumed by controls. We found that aging induced a reduction of the total number of NPY- and SS-positive neurons in the hippocampal formation accompanied by a decrease of the cholinergic varicosities. Conversely, the 24-month-old-onset caloric-restricted animals maintained the number of those peptidergic neurons and the density of the cholinergic varicosities similar to the 12-month control rats. These results suggest that the aging-associated reduction of these neuropeptide-expressing neurons is not due to neuronal loss and may be dependent of the cholinergic system. More importantly, caloric restriction has beneficial effects in the NPY- and SS-expressing neurons and in the cholinergic system, even when applied in old age.