Restraint-Induced Expression of Endoplasmic Reticulum Stress-Related Genes in the Mouse Brain

Mitsue Ishisaka, Takashi Kudo, Masamitsu Shimazawa, Kenichi Kakefuda, Atsushi Oyagi, Kana Hyakkoku, Kazuhiro Tsuruma, Hideaki Hara

.

DOI: 10.4236/pp.2011.21002                

Abstract

Depression is a significant public health concern but its pathology remains unclear. Previously, increases in an endoplasmic reticulum (ER) stress-related protein were reported in the temporal cortex of subjects with major depressive disorder who had died by suicide. This finding suggests an association between depression and ER stress. The present study was designed to investigate whether acute stress could affect the ER stress response. Mice were immobilized for a period of 6 hr and then expression of ER stress response-related genes was measured by real-time PCR. We also used enzyme-linked immunosorbent assay for concomitant measurement of the plasma corticosterone levels in the mice. The effect of corticosterone on ER stress proteins was further investigated by treating mice with corticosterone for 2 weeks and then measuring ER protein expression by Western blotting. After a 6 hr restraint stress, mRNA levels of ER stress-related genes, such as the 78-kilodalton glucose regulated protein (GRP78), the 94-kilodalton glucose regulated protein (GRP94), and calreticulin, were increased in the cortex, hippocampus, and striatum of mouse brain. Blood plasma corticosterone level was also increased. In the corticosterone-treated mouse model, the expression of GRP78 and GRP94 was significantly increased in the hippocampus. These results suggest that acute stress may affect ER function and that ER stress may be involved in the pathogenesis of restraint stress, including the development of depression.

Keywords

Corticosterone, Depression, Endoplasmic Reticulum Stress, Restraint Stress

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	R. C. Kessler, P. Berglund, O. Demler, R. Jin, K. R. Me-rikangas and E. E. Walters, “Lifetime Prevalence and Age-of-onset Distributions of DSM-IV Disorders in the National Comorbidity Survey Replication,” Archives of general psychiatry, Vol. 62, No. 6, 2005, pp. 593-602. doi:10.1001/archpsyc.62.6.593
[2]	D. Ron and P. Walter, “Signal Integration in the Endo-plasmic Reticulum Unfolded Protein Response,” Nature reviews, Vol. 8, No. 7, 2007, pp. 519-529.
[3]	V. I. Rasheva and P. M. Domingos, “Cellular Responses to Endoplasmic Reticulum Stress and Apoptosis,” Apoptosis, Vol. 14, No. 8, 2009, pp. 996-1007. doi: 10.1007/s10495-009-0341-y
[4]	S. Oyadomari and M. Mori, “Roles of CHOP/GADD153 in Endoplasmic Reticulum Stress,” Cell Death and Differentiation, Vol. 11, No. 4, 2004, pp. 381-389. doi: 10.1038/sj.cdd.4401373
[5]	R. S. Saliba, P. M. Munro, P. J. Luthert and M. E. Chee-tham, “The Cellular Fate of Mutant Rhodopsin: Quality Control, Degradation and Aggresome Formation,” Journal of cell science, Vol. 115, No. Pt 14, 2002, pp. 2907-2918.
[6]	E. H. Koo, P. T. Lansbury, Jr. and J. W. Kelly, “Amyloid Diseases: Abnormal Protein Aggregation in Neurodegeneration,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 96, No. 18, 1999, pp. 9989-9990. doi:10.1073/pnas.96.18.9989
[7]	C. Kakiuchi, K. Iwamoto, M. Ishiwata, M. Bundo, T. Kasahara, I. Kusumi, T. Tsujita, Y. Okazaki, S. Nanko, H. Kunugi, T. Sasaki and T. Kato, “Impaired Feedback Regulation of XBP1 as a Genetic Risk Factor for Bipolar disorder,”Nature Genetics, Vol. 35, No. 2, 2003, pp. 171-175. doi:10.1038/ng1235
[8]	C. Kakiuchi, M. Ishiwata, T. Umekage, M. Tochigi, K. Kohda, T. Sasaki and T. Kato, “Association of the XBP1- 116C/G Polymorphism with Schizophrenia in the Japanese Population,” Psychiatry and Clinical Neurosciences, Vol. 58, No. 4, 2004, pp. 438-440. doi:10.1111/j.1440-1819.2004.01280.x
[9]	L. Shao, X. Sun, L. Xu, L. T. Young and J. F. Wang, “Mood Stabilizing Drug Lithium Increases Expression of Endoplasmic Reticulum Stress Proteins in Primary Cultured Rat Cerebral Cortical Cells,” Life Sciences, Vol. 78, No. 12, 2006, pp. 1317-1323. doi:10.1016/j.lfs.2005.07.007
[10]	S. Kurosawa, E. Hashimoto, W. Ukai, S. Toki, S. Saito and T. Saito, “Olanzapine Potentiates Neuronal Survival and Neural Stem Cell Differentiation: Regulation of Endo-plasmic Reticulum Stress Response Proteins,” Journal of Neural Transmission, Vol. 114, No. 9, 2007, pp. 1121-1128. doi:10.1007/s00702-007-0747-z
[11]	C. Bown, J. F. Wang, G. MacQueen and L. T. Young, “Increased Temporal Cortex ER Stress Proteins in Depressed Subjects Who Died by Suicide,” Neuropsychopharmacology, Vol. 22, No. 3, 2000, pp. 327-332. doi:10.1016/S0893-133X(99)00091-3
[12]	Y. I. Sheline, P. W. Wang, M. H. Gado, J. G. Csernansky and M. W. Vannier, “Hippocampal Atrophy in Recurrent Major Depression,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 93, No. 9, 1996, pp. 3908-3913. doi:10.1073/pnas.93.9.3908
[13]	D. Ongur, W. C. Drevets and J. L. Price, “Glial Reduction in the Subgenual Prefrontal Cortex in Mood Disorders,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 95, No. 22, 1998, pp. 13290-13295. doi:10.1073/pnas.95.22.13290
[14]	Y. Watanabe, E. Gould and B. S. McEwen, “Stress Induces Atrophy of Apical Dendrites of Hippocampal CA3 Pyramidal Neurons,” Brain research, Vol. 588, No. 2, 1992, pp. 341-345. doi:10.1016/0006-8993(92)91597-8
[15]	A. Bachis, M. I. Cruz, R. L. Nosheny and I. Mocchetti, “Chronic Unpredictable Stress Promotes Neuronal Apoptosis in the Cerebral Cortex,” Neuroscience Letters, Vol. 442, No. 2, 2008, pp. 104-108.
[16]	D. Chen, E. Padiernos, F. Ding, I. S. Lossos and C. D. Lopez, “Apoptosis-stimulating Protein of P53-2 (ASPP2/ 53BP2L) is an E2F Target Gene,” Cell Death and Differentiation, Vol. 12, No. 4, 2005, pp. 358-368. doi:10.1038/sj.cdd.4401536
[17]	O. I. Abatan, K. B. Welch and J. A. Nemzek, “Evaluation of Saphenous Venipuncture and Modified Tail-clip Blood Collection in Mice,” Journal of the American Association for Laboratory Animal Science,, Vol. 47, No. 3, 2008, pp. 8-15.
[18]	S. L. Gourley and J. R. Taylor, “Recapitulation and Reversal of a Persistent Depression-like Syndrome in Rodents,” Current Protocols in Neuroscience Chapter 9, 2009, Unit-9.32.
[19]	X. Z. Wang, B. Lawson, J. W. Brewer, H. Zinszner, A. Sanjay, L. J. Mi, R. Boorstein, G. Kreibich, L. M. Hendershot and D. Ron, “Signals from the Stressed Endoplasmic Reticulum Induce C/EBP-homologous Protein (CHOP/GADD153),” Molecular and Cellular Biology, Vol. 16, No. 8, 1996, pp. 4273-4280.
[20]	H. Zinszner, M. Kuroda, X. Wang, N. Batchvarova, R. T. Lightfoot, H. Remotti, J. L. Stevens and D. Ron, “CHOP is Implicated in Programmed Cell Death in Response to Impaired Function of the Endoplasmic Reticulum,” Genes & Development, Vol. 12, No. 7, 1998, pp. 982-995. doi:10.1101/gad.12.7.982
[21]	M. Cechowska-Pasko, “Endoplasmic Reticulum Chaper- ons,” Postepy Biochemii, Vol. 55, No. 4, 2009, pp. 416-424.
[22]	C. A. Sandman, J. L. Barron and L. Parker, “Disregulation of Hypothalamic-pituitary-adrenal Axis in the Men- tally Retarded,” Pharmacology, Biochemistry, and Behavior, Vol. 23, No. 1, 1985, pp. 21-26. doi:10.1016/0091-3057(85)90124-8
[23]	A. Roy, “Hypothalamic-pituitary-adrenal Axis Function and Suicidal Behavior in Depression,” Biological psychiatry, Vol. 32, No. 9, 1992, pp. 812-816. doi:10.1016/0006-3223(92)90084-D
[24]	J. F. Lopez, D. M. Vazquez, D. T. Chalmers and S. J. Watson, “Regulation of 5-HT Receptors and the Hypothalamic-pituitary-adrenal Axis. Implications for the Neurobiology of Suicide,” Annals of the New York Academy of Sciences, Vol. 836, No. 1, 1997, pp. 106-134.
[25]	J. Y. Zhou, H. J. Zhong, C. Yang, J. Yan, H. Y. Wang and J. X. Jiang, “Corticosterone Exerts Immunostimulatory Effects on Macrophages via Endoplasmic Reticulum Stress,” The British Journal of Surgery, Vol. 97, No. 2, 2010, pp. 281-293. doi:10.1002/bjs.6820
[26]	J. Du, B. McEwen and H. K. Manji, “Glucocorticoid Receptors Modulate Mitochondrial Function: A Novel Mechanism for Neuroprotection,” Communicative & Integrative Biology, Vol. 2, No. 4, 2009, pp. 350-352.
[27]	J. Du, Y. Wang, R. Hunter, Y. Wei, R. Blumenthal, C. Falke, R. Khairova, R. Zhou, P. Yuan, R. Machado-Vieira, B. S. McEwen and H. K. Manji, “Dynamic Regulation of Mitochondrial Function by Glucocorticoids,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 9, 2009, pp. 3543-3548. doi:10.1073/pnas.0812671106
[28]	H. Coe and M. Michalak, “Calcium Binding Chaperones of the Endoplasmic Reticulum,” General Physiology and Biophysics, Vol. 28 Spec No Focus, 2009, pp. 96- 103.
[29]	N. Galeotti, A. Bartolini and C. Ghelardini, “Blockade of Intracellular Calcium Release Induces an Antidepressant-like Effect in the Mouse Forced Swimming Test,” Neuropharmacology, Vol. 50, No. 3, 2006, pp. 309-316. doi:10.1016/j.neuropharm.2005.09.005
[30]	S. L. Gourley, F. J. Wu, D. D. Kiraly, J. E. Ploski, A. T. Kedves, R. S. Duman and J. R. Taylor, “Regionally Specific Regulation of ERK MAP Kinase in a Model of Antidepressant-sensitive Chronic Depression,” Biological psychiatry, Vol. 63, No. 4, 2008, pp. 353-359. doi:10.1016/j.biopsych.2007.07.016
[31]	T. Ito, N. Morita, M. Nishi and M. Kawata, “In Vitro and in Vivo Immunocytochemistry for the Distribution of Mineralocorticoid Receptor with the Use of Specific Antibody,” Neuroscience Research, Vol. 37, No. 3, 2000, pp. 173-182. doi:10.1016/S0168-0102(00)00112-7
[32]	F. Han, H. Ozawa, K. Matsuda, M. Nishi and M. Kawata, “Colocalization of Mineralocorticoid Receptor and Glucocorticoid Receptor in the Hippocampus and Hypothalamus,” Neuroscience Research, Vol. 51, No. 4, 2005, pp. 371-381. doi:10.1016/j.neures.2004.12.013
[33]	P. J. Lucassen, W. Scheper and E. J. Van Someren, “Adult Neurogenesis and the Unfolded Protein Response; New Cellular and Molecular Avenues in Sleep Research,” Sleep Medicine Reviews, Vol. 13, No. 3, 2009, pp. 183-186. doi:10.1016/j.smrv.2008.12.004
[34]	G. Chen, Z. Fan, X. Wang, C. Ma, K. A. Bower, X. Shi, Z. J. Ke and J. Luo, “Brain-derived Neurotrophic Factor Suppresses Tunicamycin-induced Upregulation of CHOP in Neurons,” Journal of Neuroscience Research, Vol. 85, No. 8, 2007, pp. 1674-1684. doi:10.1002/jnr.21292