Apoptotic protein expression and activation of caspases is changed following cholinergic denervation and hippocampal sympathetic ingrowth in rat hippocampus
K. Kolasa et Le. Harrell, Apoptotic protein expression and activation of caspases is changed following cholinergic denervation and hippocampal sympathetic ingrowth in rat hippocampus, NEUROSCIENC, 101(3), 2000, pp. 541-546
Following cholinergic denervation of the hippocampus by medial septal lesio
ns, an unusual neuronal reorganization occurs in which peripheral adrenergi
c fibers arising from superior cervical ganglia grow into the hippocampus (
hippocampal sympathetic ingrowth). Recent studies suggest that a similar pr
ocess, in which sympathetic noradrenergic axons invade the hippocampus, can
occur in Alzheimer's disease patients. In the last few years, the occurren
ce of apoptotic cell death has been studied in Alzheimer's disease patients
and in animal models of this disorder. Several studies suggest that the hi
ppocampus is an important area to be considered for apoptotic cell death. I
n our studies in the rat hippocampus, we have measured the expression of in
ducers and blockers of apoptosis in membrane, cytosolic and mitochondrial f
ractions, and the activity of caspases. The level of cytosolic Fas was incr
eased in cholinergic denervation compared to control and hippocampal sympat
hetic ingrowth groups. The membrane Fas ligand expression was significantly
increased in hippocampal sympathetic ingrowth and in cholinergic denervati
on compared to the control group. The level of caspase-3 (CPP32) was increa
sed in the cholinergic denervation group compared to control and hippocampa
l sympathetic ingrowth groups. The cytosolic expression of bcl-x was increa
sed in hippocampal sympathetic ingrowth compared to control and cholinergic
denervation. The cytosolic activity of caspase-3 appeared to be significan
tly decreased in hippocampal sympathetic ingrowth and increased in choliner
gic denervation groups compared to control and cholinergic denervation/hipp
ocampal sympathetic ingrowth, respectively.
From the present results, we suggest that cholinergic denervation may be re
sponsible for pro-apoptotic responses, while hippocampal sympathetic ingrow
th may protect neurons from apoptosis in rat dorsal hippocampus. (C) 2000 I
BRO. Published by Elsevier Science Ltd. All rights reserved.