Articles

Article

Original

Exp Neurobiol 2004; 13(1): 29-37

Published online July 1, 2004

© The Korean Society for Brain and Neural Sciences

Necrosis of Neurons and Oligodendrocytes and Activation of Astrocytes and Microglia following the Intrahippocampal Injections of Zinc

Seok Jun Won1-3, Eun Young Kim1, Seonghyang Sohn3,4,Hyuk Jae Kwon4, Noh-Pal Jung5, In-Ho Choi6, Yung Keun Oh6,Hyung Cheal Shin7 and Byoung Joo Gwag1-3,*

1Center for the Interventional Therapy of Stroke and Alzheimer's Disease, Departments of 2Pharmacology and 3Neuroscience, School of Medicine, and4The Laboratory of Cell Biology, Institute for Medical Sciences, Ajou University, Suwon 442-749; 5Department of Biology, Yonsei University, Seoul; 6Department of Life Science, Yonsei University, Wonju; 7Department of Physiology,Hallym University School of Medicine, Chunchun, Korea

Correspondence to: *To whom correspondence should be addressed.
TEL: 82-31-219-5063. FAX: 82-31-219-5069
e-mail: bjgwag@madang.ajou.ac.kr

Abstract

Entry and accumulation of Zn2+ ions contribute to neuronal death following hypoxic- ischemia and traumatic brain injury. In this study, we examined patterns of cell death and activation following the intrahippocampal injections of Zn2+ in adult rat brain. The injections of 3∼20 nmole Zn2+ dose-dependently produced degeneration of the hippocampal neurons and glia over the next 24 h. Cell injury was detectable within 4 h, increased by 3 d, and disappeared within 7 d. Ultrastructural analysis demonstrated that treatment with Zn2+ caused necrotic degeneration preferentially in neurons and oligodendrocytes that was accompanied by swelling of cell body and mitochondria, early fenestration of plasma membrane, and irregularly scattered condensation of nuclear chromatin. Immunohistochemistry of glial marker proteins (glial fibrillary acidic protein for astrocytes and OX42 for microglia) revealed that astrocytes were activated bilaterally in the hippocampal formation and neocortex while microglia were activated ipsilaterally in the vicinity of the injection site 24 h later. The present study provides evidence that Zn2+ ions released under pathological conditions can injure neurons and oligo-dendrocytes exclusively through necrosis and activate astrocytes and microglia

Keywords: Zinc, necrosis, hippocampus, cortex, neuron, oligodendrocyte, astrocyte, microglia