Abstract
Study design:
Focus group study
Objective:
To investigate cell-specific endoplasmic reticulum (ER) stress reactions in contusive spinal cord by evaluating the expression of the glucose-regulated protein 78 (GRP78) and C/EBP homologous transcription factor protein (CHOP) using immunohistochemical staining.
Setting:
Data were analysed at Tokai University School of Medicine in Japan.
Methods:
The authors generated rat spinal cord injury (SCI) models using an IH-Impactor (100 kdyne(LI), 200 kdyne (HI)). Rats were killed at 1, 3, 5, 7 and 14 days post operation (dpo). Spinal cord sections were prepared and the expression ratio of GRP78 and CHOP was evaluated in oligodendrocyte precursor cells (OPCs) (NG2+), oligodendrocytes (OLs) (APC+), neurons (NeuN+) and astrocytes (GFAP+) using double immunohistochemical staining. We examined an area 8 mm distal from SCI-epicenter.
Results:
Compared with the sham group, both injured groups had higher GRP78 expression ratio in contused spinal cord at 1 dpo. GRP78 expression ratio was highest in GFAP+ cells of both groups, and lowest in NG2+ cells. Although GRP78 was expressed strongly immediately after SCI in the both groups, increased CHOP expression was observed only in the HI group. The CHOP expression in NG2+ cells was significantly higher than that observed in GFAP+ cells at 5 dpo.
Conclusion:
Although the ER stress response contributes to cell survival in the low-stress SCI conditions, the ER stress response induces an apoptotic cascade in high-stress SCI conditions. The ER response varies according to cell type, with the highest observed in astrocytes, and the lowest observed in oligodendrocyte precursor cells.
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References
Hall ED, Braughler JM . Free radicals in CNS injury. Res Publ Assoc Res Nerv Ment Dis 1993; 71: 81–105.
Tator CH, Fehlings MG . Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms. J Neurosurg 1991; 75: 15–26.
Watanabe M, Fujimura Y, Nakamura M, Yato Y, Ohta K, Okai H et al. Changes of amino acid levels and aspartate distribution in the cervical spinal cord after traumatic SCI. J Neurotrauma 1998; 15: 285–293.
Park E, Velumian AA, Fehlings MG . The role of excitotoxicity in secondary mechanisms of SCI: a review with an emphasis on the implications for white matter degeneration. J Neurotrauma 2004; 21: 754–774.
Suyama K, Watanabe M, Sakabe K, Okada Y, Matsuyama D, Kuroiwa M . Overexpression of GRP78 protects glial cells from ER stress. Neurosci Lett 2011; 504: 271–276.
Lindholm D, Wootz H, Korhonen L . ER stress and neurodegenerative diseases. Cell Death Differ 2006; 13: 385–392.
Penas C, Guzman MS, Verdu E, Fores J, Navarro X, Casas C . Spinal cord injury induces ER stress with different cell-type dependent response. J Neurochem 2007; 102: 1242–1255.
Lee AS . The ER chaperone and signalling regulator GRP78/BiP as a monitor of endoplasmic reticulum stress. Methods 2005; 35: 373–381.
Deslauriers AM, Afkhami-Goli A, Paul AM, Bhat RK, Acharjee S, Ellestad KK et al. Neuroinflammation and ER stress are coregulated by crocin to prevent demyelination and neurodegeneration. J Immunol 2011; 187: 4788–4799.
Haas IG . BiP (GRP78), an essential hsp70 resident protein in the ER. Experientia 1994; 50: 1012–1020.
Walter P, Ron D . The unfolded protein response: from stress pathway to homeostatic regulation. Science 2011; 334: 1081–1086.
Wang Z, Zhang C, Hong Z, Chen H, Chen W, Chen G . C/EBP homologous protein (CHOP) mediates neuronal apoptosis in rats with spinal cord injury. Experimental and Therapeutic Med 2013; 5: 107–111.
Scheff SW, Rabchevsky AG, Fugaccia I, Main JA, Lumpp JE Jr . Experimental modeling of SCI: characterization of a force-defined injury device. J Neurotrauma 2003; 20: 179–193.
Li GL, Farooque M, Holtz A, Olsson Y . Apoptosis of oligodendrocytes occurs for long distances away from the primary injury after compression trauma to rat spinal cord. Acta Neuropathol 1999; 98: 473–480.
Ohri SS, Maddie MA, Zhao Y, Qiu MS, Hetman M, Whittemore SR . Attenuating the endoplasmic reticulum stress response improves functional recovery after spinal cord injury. Glia 2011; 59: 1489–1502.
Nash B, Thomson CE, Linington C, Arthur AT, McClure JD, McBride MW et al. Functional duality of astrocytes in myelination. J Neurosci 2011; 31: 13028–13038.
McTigue D, Richa T, Ping W . NG2 Colocalizes With Axons and Is Expressed by a Mixed Cell Population in Spinal Cord Lesions. J Neuropathol Exp Neurol 2006; 65: 406–4207.
Watanabe M, Toyama Y, Nishiyama A . Differentiation of proliferated NG2-positive glial progenitor cells in a remyelinating lesion. J Neurosci Res 2002; 69: 826–836.
Schroder M, Kaufman RJ . ER stress and the unfolded protein response. Mutat Res 2005; 569: 29–63.
Saito A, Hino S, Murakami T, Kondo S, Imaizumi K . A novel ER stress transducer, OASIS, expressed in astrocytes. Antioxid Redox Signal 2007; 9: 563–571.
Acknowledgements
This work was supported in part by Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan (21591907).
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Matsuyama, D., Watanabe, M., Suyama, K. et al. Endoplasmic reticulum stress response in the rat contusive spinal cord injury model-susceptibility in specific cell types. Spinal Cord 52, 9–16 (2014). https://doi.org/10.1038/sc.2013.118
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DOI: https://doi.org/10.1038/sc.2013.118
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