The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Increase of Synapsin I, Phosphosynapsin (ser-9), and GAP-43 in the Rat Hippocampus after Middle Cerebral Artery Occlusion

  • Jung, Yeon-Joo (Department of Pharmacology and Medical Research Institute, College of Medicine, Ewha Womans University) ;
  • Huh, Pil-Woo (Department of Neurosurgery, The Catholic University of Korea, Uijongbu St. Mary's Hospital) ;
  • Park, Su-Jin (Department of Pharmacology and Medical Research Institute, College of Medicine, Ewha Womans University) ;
  • Park, Jung-Sun (Department of Pharmacology and Medical Research Institute, College of Medicine, Ewha Womans University) ;
  • Lee, Kyung-Eun (Department of Pharmacology and Medical Research Institute, College of Medicine, Ewha Womans University)
  • Published : 2004.04.21
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Abstract

The loss of neurons and synaptic contacts following cerebral ischemia may lead to a synaptic plastic modification, which may contribute to the functional recovery after a brain lesion. Using synapsin I and GAP-43 as markers, we investigated the neuronal cell death and the synaptic plastic modification in the rat hippocampus of a middle cerebral artery occlusion (MCAO) model. Cresyl violet staining revealed that neuronal cell damage occurred after 2 h of MCAO, which progressed during reperfusion for 2 weeks. The immunoreactivity of synapsin I and GAP-43 was increased in the stratum lucidum in the CA3 subfield as well as in the inner and outer molecular layers of dentate gyrus in the hippocampus at reperfusion for 2 weeks. The immunoreactivity of phosphosynapsin was increased in the stratum lucidum in the CA3 subfield during reperfusion for 1 week. Our data suggest that the increase in the synapsin I and GAP-43 immunoreactivity probably mediates either the functional adaptation of the neurons through reactive synaptogenesis from the pre-existing presynaptic nerve terminals or the structural remodeling of their axonal connections in the areas with ischemic loss of target cells. Furthermore, phosphosynapsin may play some role in the synaptic plastic adaptations before or during reactive synaptogenesis after the MCAO.

Keywords

References

  1. Bernabeu R, Sharp FR. NMDA and AMPA/Kainate glutamate receptors modulate dentate neurogenesis and CA3 synapsin I in normal and ischemic hippocampus. J Cerebral Blood Flow Metab 20: 1669-1680, 2000 https://doi.org/10.1097/00004647-200012000-00006
  2. Bolay H, Gürsoy-Özdemir Y, Sara Y, Onur R, Can A, Dalkara T. Persistant defect in transmitter release and synapsin phosphorylation in cerebral cortex after transient moderate ischemic injury. Stroke 33: 1369-1375, 2002 https://doi.org/10.1161/01.STR.0000013708.54623.DE
  3. Butler T, Kassed C, Sanberg PR, Willing AE, Pennypacker KR. Neurodegeneration in the rat hippocampus and striatum after middle cerebral artery occlusion. Brain Res 929: 252-260, 2002 https://doi.org/10.1016/S0006-8993(01)03371-6
  4. Chopp M, Li Y, Jiang N. Increase in apoptosis and concomitant reduction of ischemic lesion volume and evidence for synaptogenesis after transient focal cerebral ischemia in rat treated with staurosporine. Brain Res 828:197-201, 1999 https://doi.org/10.1016/S0006-8993(99)01354-2
  5. Dailey M, Buchanan J, Bergles DE, Smith SJ. Mossy fiber growth and synaptogenesis in rat hippocampal slices in vitro. J Neurosci 14: 1060-1078, 1994
  6. Fujie W, Kirino T, Tomukai N, Iwasawa T, Tamura A. Progressive shrinkage of the thalamus following middle cerebral artery occlusion in rats. Stroke 21: 1485-1488, 1990 https://doi.org/10.1161/01.STR.21.10.1485
  7. Greengard P, Valtorta F, Czernik AJ, Benfenati F. Synaptic vesicle phosphoproteins and regulation of synaptic function. Science 259: 780-785, 1993 https://doi.org/10.1126/science.8430330
  8. Gregersen R, Christensen T, Lehrmann E, Diemer NH, Finsen B. Focal cerebral ischemia induces increased myelin basic protein and growth associated protein-43 gene transduction in periinfarct areas in the rat brain. Exp Brain Res 138: 384-392, 2001 https://doi.org/10.1007/s002210100715
  9. Hoff SF. Lesion-induced transneuronal plasticity in the adult rat hippocampus. Neuroscience 19: 1227-1232, 1986 https://doi.org/10.1016/0306-4522(86)90136-3
  10. Huang KP, Huang FL, Chen HC. Hypoxia/ischemia induces dephosphorylation of rat brain neuromodulin/GAP-43 in vivo. J Neurochem 72: 1294-1306, 1999 https://doi.org/10.1046/j.1471-4159.1999.0721294.x
  11. Huh PW, Belayev L, Zhao W, Busto R, Saul I, Ginsberg MD. The effect of high dose albumin therapy on local cerebral perfusion after transient focal cerebral ischemia in rats. Brain Res 804: 105-113, 1998 https://doi.org/10.1016/S0006-8993(98)00674-X
  12. Kitagawa K, Matsumoto M, Hori M. Protective and regenerative response endogenously induced in the ischemic brain. Can J Pharmacol 79: 262-265, 2001 https://doi.org/10.1139/cjpp-79-3-262
  13. Koizumi J, Yoshida Y, Nazakawa T, Oneda G. Experimental studies of ischemic brain edema, I: a new experimental model of cerebral embolism in rats in which recirculation can be introduced in the ischemic area. Jpn J Stroke 8: 1-8, 1986 https://doi.org/10.3995/jstroke.8.1
  14. Li Y, Jiang N, Powers C, Chopp M. Neuronal damage and plasticity identified by microtubule-associated protein 2, growth-associated protein 43, and cyclin D1 immunoreactivity after focal cerebral ischemia in rats. Stroke 29: 1972-1981, 1998 https://doi.org/10.1161/01.STR.29.9.1972
  15. Marti E, Ferrer I, Blasi J. Transient increase of synapsin I immunoreactivity in the mossy fiber layer of the hippocampus after transient forebrain ischemia in the Mongolian gerbil. Brain Res 824: 153-160, 1999 https://doi.org/10.1016/S0006-8993(99)01158-0
  16. Menegon A, Dunlap DD, Castano F, Benfenati F, Czernik AJ, Greengard P, Valtorta F. Use of phosphosynapsin I-specific antibodies for image analysis of signal transduction in single nerve terminals. J Cell Sci 113: 3573-3582, 2000
  17. Schmidt-Kastner R, Bedard A, Hakim A. Transient expression of GAP-43 within the hippocampus after global brain ischemia in rat. Cell Tissue Res 288: 225-238, 1997 https://doi.org/10.1007/s004410050808
  18. Schmidt-Kastner R, Freund TF. Selective vulnerability of the hippocampus in brain ischemia. Neuroscience 40: 599-636, 1991 https://doi.org/10.1016/0306-4522(91)90001-5
  19. Sopala M, Frankiewicz T, Parsons C, Danysz W. Middle cerebral artery occlusion produces secondary, remote impairment in hippocampal plasticity of rats-involvement of N-methyl-D-aspartate receptors. Neurosci Lett 281: 143-146, 2000 https://doi.org/10.1016/S0304-3940(00)00829-6
  20. Stroemer RP, Kent TA, Hulsebosch CE. Enhanced neocortical neural sprouting, synaptogenesis, and behavioral recovery with D-amphetamine therapy after neocortical infarction in rats. Stroke 29: 2381-2395, 1998 https://doi.org/10.1161/01.STR.29.11.2381
  21. Tagaya M, Matsuyama T, Nakamura H, Hata R, Shimizu S, Kiyama H, Matsumoto M, Sugita M. Increased F1/GAP-43 mRNA accumulation in gerbil hippocampus after brain ischemia. J Cereb Blood Flow Metab 15: 1132-1136, 1995 https://doi.org/10.1038/jcbfm.1995.140