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Restraint Stress in Rats Alters Gene Transcription and Protein Translation in the Hippocampus

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Abstract

Stress is a relatively new and emerging risk factor for Alzheimer’s disease (AD). Severe stress can alter brain characteristics such as neuronal plasticity, due to changes in the metabolism of cytoskeletal proteins. In this study, male Wistar rats were exposed to restraint stress (RS) for 5 h daily for different time periods. At the end of the exposure periods, the amounts of β-actin, cofilin, amyloid precursor protein (APP) and mitogen-activated protein kinase 1 (MAPK-1) RNAs and proteins were investigated. The mRNA expressions of β-actin, cofilin and MAPK-1 followed U-shaped time course. Acute (3 days) and chronic (21 days) RS caused a fourfold and tenfold increases, respectively, in hippocampal β-actin mRNA expression. In the case of cofilin mRNA expression, elevations were detected in the hippocampus on days 3, 7 and 21. The APP mRNA level was increased on day 21. On protein level, chronic stress elevated the levels of β-actin, cofilin and APP in the hippocampus. These results suggest that stress causes the induction of some genes and proteins that are also elevated in AD selectively in the hippocampal region of the rat brain.

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References

  1. Alberini CM (2006) Unwind: chronic stress exacerbates the deficits of Alzheimer’s disease. Biol Psychiatry 65:916–917

    Article  Google Scholar 

  2. Chen Y, Dube CM, Rice CJ, Baram TZ (2008) Rapid loss of dendritic spines after stress involves derangement of spine dynamics by corticotropin-releasing hormone. J Neurosci 28:2903–2911

    Article  PubMed  CAS  Google Scholar 

  3. Baloyannis SJ (2009) Dendritic pathology in Alzheimer’s disease. J Neurol Sci 283:153–157

    Article  PubMed  CAS  Google Scholar 

  4. Dong H, Csernansky JG (2009) Effects of stress and stress hormones on amyloid-beta protein and plaque deposition. J Alzheimers Dis 18:459–469

    PubMed  CAS  Google Scholar 

  5. Lee KW, Kim JB, Seo JS, Kim TK, Im JY, Baek IS, Kim KS, Lee JK, Han PL (2009) Behavioral stress accelerates plaque pathogenesis in the brain of Tg2576 mice via generation of metabolic oxidative stress. J Neurochem 108:165–175

    Article  PubMed  CAS  Google Scholar 

  6. Devi L, Alldred MJ, Ginsberg SD, Ohno M (2010) Sex- and brain region-specific acceleration of beta-amyloidogenesis following behavioral stress in a mouse model of Alzheimer’s disease. Mol Brain 3:34

    Article  PubMed  Google Scholar 

  7. Alkadhi KA, Alzoubi KH, Srivareerat M, Tran TT (2011) Elevation of BACE in an Abeta rat model of Alzheimer’s disease: exacerbation by chronic stress and prevention by nicotine. Int J Neuropsychopharmacol 28:1–11

    Google Scholar 

  8. Tran TT, Srivareerat M, Alkadhi KA (2010) Chronic psychosocial stress triggers cognitive impairment in a novel at-risk model of Alzheimer’s disease. Neurobiol Dis 37:756–763

    Article  PubMed  CAS  Google Scholar 

  9. Wilson RS, Barnes LL, Bennett DA, Li Y, Bienias JL, Mendes de Leon CF, Evans DA (2005) Proneness to psychological distress and risk of Alzheimer disease in a biracial community. Neurology 64:380–382

    Article  PubMed  CAS  Google Scholar 

  10. Caballero J, Hitchcock M, Beversdorf D, Scharre D, Nahata M (2006) Long-term effects of antidepressants on cognition in patients with Alzheimer’s disease. J Clin Pharm Ther 31:593–598

    Article  PubMed  CAS  Google Scholar 

  11. Csernansky JG, Dong H, Fagan AM, Wang L, Xiong C, Holtzman DM, Morris JC (2006) Plasma cortisol and progression of dementia in subjects with Alzheimer-type dementia. Am J Psychiatry 163:2164–2169

    Article  PubMed  Google Scholar 

  12. Bao AM, Meynen G, Swaab DF (2008) The stress system in depression and neurodegeneration: focus on the human hypothalamus. Brain Res Rev 57:531–553

    Article  PubMed  CAS  Google Scholar 

  13. Sekino Y, Kojima N, Shirao T (2007) Role of actin cytoskeleton in dendritic spine morphogenesis. Neurochem Int 51:92–104

    Article  PubMed  CAS  Google Scholar 

  14. Bamburg JR, Bloom GS (2009) Cytoskeletal pathologies of Alzheimer disease. Cell Motil Cytoskeleton 66:635–649

    Article  PubMed  CAS  Google Scholar 

  15. Maloney MT, Minamide LS, Kinley AW, Boyle JA, Bamburg JR (2005) Beta-secretase-cleaved amyloid precursor protein accumulates at actin inclusions induced in neurons by stress or amyloid beta: a feedforward mechanism for Alzheimer’s disease. J Neurosci 25:11313–11321

    Article  PubMed  CAS  Google Scholar 

  16. Hirano A (1994) Hirano bodies and related neuronal inclusions. Neuropathol Appl Neurobiol 20:3–11

    Article  PubMed  CAS  Google Scholar 

  17. Haass C, Selkoe DJ (1993) Cellular processing of beta-amyloid precursor protein and the genesis of amyloid beta-peptide. Cell 75:1039–1042

    Article  PubMed  CAS  Google Scholar 

  18. Golde TE, Eckman CB, Younkin SG (2000) Biochemical detection of Abeta isoforms: implications for pathogenesis, diagnosis, and treatment of Alzheimer’s disease. Biochim Biophys Acta 1502:172–187

    PubMed  CAS  Google Scholar 

  19. Ferreira ST, Vieira MN, De Felice FG (2007) Soluble protein oligomers as emerging toxins in Alzheimer’s and other amyloid diseases. IUBMB Life 59:332–345

    Article  PubMed  CAS  Google Scholar 

  20. Krafft GA, Klein WL (2010) ADDLs and the signaling web that leads to Alzheimer’s disease. Neuropharmacology 59:230–242

    Article  PubMed  CAS  Google Scholar 

  21. Medeiros R, Baglietto-Vargas D, Laferla FM (2011) The role of Tau in Alzheimer’s disease and related disorders. CNS Neurosci Ther 17:514–524

    Article  PubMed  CAS  Google Scholar 

  22. Huang HC, Jiang ZF (2009) Accumulated amyloid-beta peptide and hyperphosphorylated tau protein: relationship and links in Alzheimer’s disease. J Alzheimers Dis 16:15–27

    PubMed  CAS  Google Scholar 

  23. Pitman DL, Ottenweller JE, Natelson BH (1988) Plasma corticosterone levels during repeated presentation of two intensities of restraint stress: chronic stress and habituation. Physiol Behav 43:47–55

    Article  PubMed  CAS  Google Scholar 

  24. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25:402–408

    Article  PubMed  CAS  Google Scholar 

  25. Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, Fujimoto EK, Goeke NM, Olson BJ, Klenk DC (1985) Measurement of protein using bicinchoninic acid. Anal Biochem 150:76–85

    Article  PubMed  CAS  Google Scholar 

  26. Magarinos AM, Orchinik M, McEwen BS (1998) Morphological changes in the hippocampal CA3 region induced by non-invasive glucocorticoid administration: a paradox. Brain Res 809:314–318

    Article  PubMed  CAS  Google Scholar 

  27. Zafir A, Banu N (2009) Modulation of in vivo oxidative status by exogenous corticosterone and restraint stress in rats. Stress 12:167–177

    Article  PubMed  CAS  Google Scholar 

  28. Murakami S, Imbe H, Morikawa Y, Kubo C, Senba E (2005) Chronic stress, as well as acute stress, reduces BDNF mRNA expression in the rat hippocampus but less robustly. Neurosci Res 53:129–139

    Article  PubMed  CAS  Google Scholar 

  29. Donohue HS, Gabbott PL, Davies HA, Rodriguez JJ, Cordero MI, Sandi C, Medvedev NI, Popov VI, Colyer FM, Peddie CJ, Stewart MG (2006) Chronic restraint stress induces changes in synapse morphology in stratum lacunosum-moleculare CA1 rat hippocampus: a stereological and three-dimensional ultrastructural study. Neuroscience 140:597–606

    Article  PubMed  CAS  Google Scholar 

  30. Andrianantoandro E, Pollard TD (2006) Mechanism of actin filament turnover by severing and nucleation at different concentrations of ADF/cofilin. Mol Cell 24:13–23

    Article  PubMed  CAS  Google Scholar 

  31. Van Troys M, Huyck L, Leyman S, Dhaese S, Vandekerkhove J, Ampe C (2008) Ins and outs of ADF/cofilin activity and regulation. Eur J Cell Biol 87:649–667

    Article  PubMed  Google Scholar 

  32. Edelstein-Keshet L, Ermentrout GB (2000) Models for spatial polymerization dynamics of rod-like polymers. J Math Biol 40:64–96

    Article  PubMed  CAS  Google Scholar 

  33. Bernstein BW, Bamburg JR (2010) ADF/cofilin: a functional node in cell biology. Trends Cell Biol 20:187–195

    Article  PubMed  CAS  Google Scholar 

  34. Rosa ML, Guimaraes FS, de Oliveira RM, Padovan CM, Pearson RC, Del Bel EA (2005) Restraint stress induces beta-amyloid precursor protein mRNA expression in the rat basolateral amygdala. Brain Res Bull 65:69–75

    Article  PubMed  CAS  Google Scholar 

  35. Catania C, Sotiropoulos I, Silva R, Onofri C, Breen KC, Sousa N, Almeida OF (2009) The amyloidogenic potential and behavioral correlates of stress. Mol Psychiatry 14:95–105

    Article  PubMed  CAS  Google Scholar 

  36. Ray B, Gaskins DL, Sajdyk TJ, Spence JP, Fitz SD, Shekhar A, Lahiri DK (2011) Restraint stress and repeated corticotrophin-releasing factor receptor activation in the amygdala both increase amyloid-beta precursor protein and amyloid-beta peptide but have divergent effects on brain-derived neurotrophic factor and pre-synaptic proteins in the prefrontal cortex of rats. Neuroscience 184:139–150

    Article  PubMed  CAS  Google Scholar 

  37. Yan J, Sun XB, Wang HQ, Zhao H, Zhao XY, Xu YX, Guo JC, Zhu CQ (2010) Chronic restraint stress alters the expression and distribution of phosphorylated tau and MAP2 in cortex and hippocampus of rat brain. Brain Res 1347:132–141

    Article  PubMed  CAS  Google Scholar 

  38. Maier T, Güell M, Serrano L (2009) Correlation of mRNA and protein in complex biological samples. FEBS Lett 583:3966–3973

    Article  PubMed  CAS  Google Scholar 

  39. Müller HK, Wegener G, Popoli M, Elfving B (2011) Differential expression of synaptic proteins after chronic restraint stress in rat prefrontal cortex and hippocampus. Brain Res 1385:26–37

    Article  PubMed  Google Scholar 

  40. Sapolsky RM, Krey LC, McEwen BS (1985) Prolonged glucocorticoid exposure reduces hippocampal neuron number: implications for aging. J Neurosci 5:1222–1227

    PubMed  CAS  Google Scholar 

  41. Sapolsky RM, Krey LC, McEwen BS (1986) The neuroendocrinology of stress and aging: the glucocorticoid cascade hypothesis. Endocr Rev 7:284–301

    Article  PubMed  CAS  Google Scholar 

  42. Derks NM, Muller M, Gaszner B, Tilburg-Ouwens DT, Roubos EW, Kozicz LT (2008) Housekeeping genes revisited: different expressions depending on gender, brain area and stressor. Neuroscience 156:305–309

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported by grants from OTKA (83667), ETT (052-07/2/2009) and the Hungarian Ministry of Education and Culture (TÁMOP 4.2.2-08/1-2008-0002, TÁMOP 4.2.1./B-09/1/KONV-2010-0005-3).

Conflict of interest

The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Psychiatry, Alzheimer’s Disease Research Centre, University of Szeged, Kálvária sgt. 57, 6701, Szeged, Hungary

    Petra Sántha, Magdolna Pákáski, Örsike Csilla Fazekas, Eszter Klára Fodor, Sára Kálmán, János Kálmán Jr, Zoltán Janka & János Kálmán

  2. Department of Pathophysiology, University of Szeged, Semmelweis St. 1, 6725, Szeged, Hungary

    Gyula Szabó

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  1. Petra Sántha
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  2. Magdolna Pákáski
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  3. Örsike Csilla Fazekas
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Correspondence to Petra Sántha.

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Sántha, P., Pákáski, M., Fazekas, Ö.C. et al. Restraint Stress in Rats Alters Gene Transcription and Protein Translation in the Hippocampus. Neurochem Res 37, 958–964 (2012). https://doi.org/10.1007/s11064-011-0688-7

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  • DOI: https://doi.org/10.1007/s11064-011-0688-7

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