Apoptotic protein expression and activation of caspases is changed following cholinergic denervation and hippocampal sympathetic ingrowth in rat hippocampus

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.