Postischemic Alterations of BDNF, NGF, HSP 70 and Ubiquitin Immunoreactivity in the Gerbil Hippocampus: Pharmacological Approach

Overview

Journal Cell Mol Neurobiol

Publisher Springer

Specialties Cell Biology
Molecular Biology
Neurology

Date 2006 Jul 1

PMID 16810563

Citations 6

Authors

Toshiki Himeda

Hiroko Tounai

Natsumi Hayakawa

Tsutomu Araki

Affiliations

Soon will be listed here.

Abstract

1. We investigated the immunohistochemical alterations of BDNF, NGF, HSP 70 and ubiquitin in the hippocampus 1 h to 14 days after transient cerebral ischemia in gerbils. We also examined the effect of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor pitavastatin against the changes of BDNF, NGF, HSP 70 and ubiquitin in the hippocampus after cerebral ischemia in the hippocampus after ischemia. 2. The transient cerebral ischemia was carried out by clamping the carotid arteries with aneurismal clips for 5 min. 3. In the present study, the alteration of HSP 70 and ubiquitin immunoreactivity in the hippocampal CA1 sector was more pronounced than that of BDNF and NGF immunoreactivity after transient cerebral ischemia. In double-labeled immunostainings, BDNF, NGF and ubiquitin immunostaining was observed both in GFAP-positive astrocytes and MRF-1-positive microglia in the hippocampal CA1 sector after ischemia. Furthermore, prophylactic treatment with pitavastatin prevented the damage of neurons with neurotrophic factor and stress proteins in the hippocampal CA1 sector after ischemia. 4. These findings suggest that the expression of stress protein including HSP 70 and ubiquitin may play a key role in the protection against the hippocampal CA1 neuronal damage after transient cerebral ischemia in comparison with the expression of neurotrophic factor such as BDNF and NGF. The present findings also suggest that the glial BDNF, NGF and ubiquitin may play some role for helping surviving neurons after ischemia. Furthermore, our present study indicates that prophylactic treatment with pitavastatin can prevent the damage of neurons with neurotrophic factor and stress proteins in the hippocampal CA1 sector after transient cerebral ischemia. Thus our study provides further valuable information for the pathogenesis after transient cerebral ischemia.

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References

Morimoto T, Ide T, Ihara Y, Tamura A, Kirino T . Transient ischemia depletes free ubiquitin in the gerbil hippocampal CA1 neurons. Am J Pathol. 1996; 148(1):249-57. PMC: 1861594. View

Kato H, Chen T, Liu X, Nakata N, Kogure K . Immunohistochemical localization of ubiquitin in gerbil hippocampus with induced tolerance to ischemia. Brain Res. 1993; 619(1-2):339-43. DOI: 10.1016/0006-8993(93)91631-2. View

Schabitz W, Sommer C, Zoder W, Kiessling M, Schwaninger M, Schwab S . Intravenous brain-derived neurotrophic factor reduces infarct size and counterregulates Bax and Bcl-2 expression after temporary focal cerebral ischemia. Stroke. 2000; 31(9):2212-7. DOI: 10.1161/01.str.31.9.2212. View

Wojcik C, Di Napoli M . Ubiquitin-proteasome system and proteasome inhibition: new strategies in stroke therapy. Stroke. 2004; 35(6):1506-18. DOI: 10.1161/01.STR.0000126891.93919.4e. View

Kato H, Kogure K, Araki T, Itoyama Y . Graded expression of immunomolecules on activated microglia in the hippocampus following ischemia in a rat model of ischemic tolerance. Brain Res. 1995; 694(1-2):85-93. DOI: 10.1016/0006-8993(95)00769-m. View

Beck T, Lindholm D, Castren E, Wree A . Brain-derived neurotrophic factor protects against ischemic cell damage in rat hippocampus. J Cereb Blood Flow Metab. 1994; 14(4):689-92. DOI: 10.1038/jcbfm.1994.86. View

Xu L, Giffard R . HSP70 protects murine astrocytes from glucose deprivation injury. Neurosci Lett. 1997; 224(1):9-12. DOI: 10.1016/s0304-3940(97)13444-9. View

Mori H, Kondo J, Ihara Y . Ubiquitin is a component of paired helical filaments in Alzheimer's disease. Science. 1987; 235(4796):1641-4. DOI: 10.1126/science.3029875. View

Kirino T . Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res. 1982; 239(1):57-69. DOI: 10.1016/0006-8993(82)90833-2. View

10.

Kaesemeyer W, Caldwell R, Huang J, Caldwell R . Pravastatin sodium activates endothelial nitric oxide synthase independent of its cholesterol-lowering actions. J Am Coll Cardiol. 1999; 33(1):234-41. DOI: 10.1016/s0735-1097(98)00514-2. View

11.

Papadopoulos M, Sun X, Cao J, Mivechi N, Giffard R . Over-expression of HSP-70 protects astrocytes from combined oxygen-glucose deprivation. Neuroreport. 1996; 7(2):429-32. DOI: 10.1097/00001756-199601310-00013. View

12.

Finley D, Ozkaynak E, Varshavsky A . The yeast polyubiquitin gene is essential for resistance to high temperatures, starvation, and other stresses. Cell. 1987; 48(6):1035-46. DOI: 10.1016/0092-8674(87)90711-2. View

13.

Muramatsu Y, Kurosaki R, Kato H, Araki T . Effect of pitavastatin against expression of S100beta protein in the gerbil hippocampus after transient cerebral ischaemia. Acta Physiol Scand. 2004; 182(1):95-107. DOI: 10.1111/j.1365-201X.2004.01300.x. View

14.

Hayashi T, Takada K, Matsuda M . Changes in ubiquitin and ubiquitin-protein conjugates in the CA1 neurons after transient sublethal ischemia. Mol Chem Neuropathol. 1991; 15(1):75-82. DOI: 10.1007/BF03161057. View

15.

Kurosaki R, Muramatsu Y, Michimata M, Matsubara M, Kato H, Imai Y . Role of nitric oxide synthase against MPTP neurotoxicity in mice. Neurol Res. 2002; 24(7):655-62. DOI: 10.1179/016164102101200717. View

16.

Araki T, Kato H, Kanai Y, Kogure K . Postischemic changes of intracellular second messengers in the gerbil brain after long-term survival: an autoradiographic study. Neuroscience. 1993; 53(3):829-36. DOI: 10.1016/0306-4522(93)90627-r. View

17.

Laufs U, La Fata V, Plutzky J, Liao J . Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation. 1998; 97(12):1129-35. DOI: 10.1161/01.cir.97.12.1129. View

18.

Aoki T, Nishimura H, Nakagawa S, Kojima J, Suzuki H, Tamaki T . Pharmacological profile of a novel synthetic inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Arzneimittelforschung. 1997; 47(8):904-9. View

19.

Yanamoto H, Mizuta I, Nagata I, Xue J, Zhang Z, Kikuchi H . Infarct tolerance accompanied enhanced BDNF-like immunoreactivity in neuronal nuclei. Brain Res. 2000; 877(2):331-44. DOI: 10.1016/s0006-8993(00)02718-9. View

20.

Yenari M, Giffard R, Sapolsky R, Steinberg G . The neuroprotective potential of heat shock protein 70 (HSP70). Mol Med Today. 1999; 5(12):525-31. DOI: 10.1016/s1357-4310(99)01599-3. View