Responses in the aged rat brain after total immunolesion.

In the present study, we compare the effects of cholinergic deafferentation of the hippocampus, cortex, and olfactory bulb of young and aged rats on nerve growth factor (NGF) protein levels in these areas. We also describe glial responses to intraventricular injections of the immunotoxin, 192 IgG-saporin in the aged. Choline acetyltransferase (ChAT) activity was dramatically decreased in the basal forebrain and target areas of the cholinergic basal forebrain neurons (CBFNs) in the young immunolesioned rats and to a lesser extent in their aged counterparts. After total immunolesion, NGF protein levels significantly increased in the hippocampus, cortex, and olfactory bulb of the young rats but not of the aged rats, except for small increases in the olfactory bulb after two weeks. After immunolesion NGF protein levels in the basal forebrain increased in young rats and less so in the aged rats. The total immunolesions had no effects on NGF and BDNF mRNA levels in the hippocampus and cortex. Two weeks after injection of the immunotoxin, the profiles of AChE- and p75NTR-positive cells significantly decreased in medial septum, vertical and horizontal limbs of diagonal band and nucleus basalis of Meynert. There was also an increase in microglia while but not astrocytes in the subnuclei of basal forebrain. In conclusion, 192 IgG-saporin was effective in producing cholinergic lesions in both young and aged rat brains, the lesion-induced NGF response was partially extinguished in the aged rat brains and immunolesions induced a microglial response in aged brain.