RESPONSES IN THE AGED RAT-BRAIN AFTER TOTAL IMMUNOLESION

In the present study, we compare the effects of cholinergic deafferent ation of the hippocampus, cortex, and olfactory bulb of young and aged rats on nerve growth factor (NGF) protein levels in these areas. We a lso describe glial responses to intraventricular injections of the imm unotoxin, 192 IgG-saporin in the aged. Choline acetyltransferase (ChAT ) activity was dramatically decreased in the basal forebrain and targe t areas of the cholinergic basal forebrain neurons (CBFNs) in the youn g immunolesioned rats and to a lesser extent in their aged counterpart s. After total immunolesion, NGF protein levels significantly increase d in the hippocampus, cortex, and olfactory bulb of the young rats but not of the aged rats, except for small increases in the olfactory bul b after two weeks. After immunolesion NGF protein levels in the basal forebrain increased in young rats and less so in the aged rats. The to tal immunolesions had no effects on NGF and BDNF mRNA levels in the hi ppocampus and cortex. Two weeks after injection of the immunotoxin, th e profiles of AChE- and p75(NTR)-positive cells significantly decrease d in medial septum, vertical and horizontal limbs of diagonal band and nucleus basalis of Meynert, There was also an increase in microglia w hile but not astrocytes in the subnuclei of basal forebrain, In conclu sion, 192 IgG-saporin was effective in producing cholinergic lesions i n both young and aged rat brains, the lesion-induced NGF response was partially extinguished in the aged rat brains and immunolesions induce d a microglial response in aged brain. J. Neurosci, Res. 54:7-16, 1998 , (C) 1998 Wiley-Liss, Inc.