Effects of Long-term Adrenalectomy on Rat Hippocampal Neurons

J Korean Neurol Assoc > Volume 16(3); 1998 > Article

Journal of the Korean Neurological Association 1998;16(3): 372-380.

장기적 부신절제술이 백서 해마 신경세포에 미치는 영향

충북대학교 의과대학 신경과학교실

Effects of Long-term Adrenalectomy on Rat Hippocampal Neurons

Seol-Heui Han, M.D.

Department of Neurology, Chungbuk National University College of Medicine

Abstract

Background: The central nervous system (CNS) is a well-known target site of steroid hormone action. Both the pyramidal neurons of Ammon's horn and the granule cells (GC) of the dentate gyrus, which have a high concentration of glucocorticoid receptors are the major targets for this hormone. Because the hippocampal formation is critically involved in memory and learning, the effects of glucocorticoid on the hippocampus are of particular interest. Chronic administration of high doses of corticosterone has been shown to directly damage to hippocampus, whereas removal of circulating glucocorticoid by adrenalectomy (ADX) may cause selective degeneration of dentate granule cells. Thus corticosterone appears to have two markedly different effects on cells of the hippocampus in rats.
Methods: In the present study, we investigate the changes in the hippocampal structures after bilateral adrenalectomy at various time points.
Results: Silver staining procedure selective for damaged neuronal membranes revealed degenerating neurons in dentate gyrus. Argyrophilia was specifically confine to dentate granule cells and was accompanied by the occurrence of pyknotic nuclei as observed in cresyl violet and H & E stained sections. However, on the contrary to the previous reports the neuronal loss in GC layers in dentate gyrus is variable. There were significant differences between individual rats in quantity of argyrophilia. In situ terminal transferase-mediated dUTP-nick end labeling technique (TUNEL) demonstrated that some of the ADX-induced neuronal degeneration was due to a apoptosis-related mechanism. In some of the ADX animals, NADPH-diaphorase positive neurons in the hippocampus found to be selectively lost. The latter finding should be confirmed in the subsequent experiments.
Conclusion: These results suggest that following ADX, some of the GC undergoes neurodegeneration via apoptotic mechanism. And the present data strengthen the evidence pointing to the critical role of corticosteroids in maintaining the structural inte Key Words: Adrenalectomy, Hippocampus, Dentate gyrus, Neurodegeneration, Apoptosis, NADPH-diaphorase