Skip to main content

Advertisement

Log in

Comparison of Glucocorticoid Receptor and Ionized Calcium-Binding Adapter Molecule 1 Immunoreactivity in the Adult and Aged Gerbil Hippocampus Following Repeated Restraint Stress

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Stress leads to changes in homeostasis and internal balance of the body and is known to be one of important factors in the development of several diseases. In the present study, we investigated changes in glucocorticoid receptor (GR) and ionized calcium-binding adapter molecule 1 (Iba-1) immunoreactivity in the adult and aged gerbil hippocampus after chronic restraint stress. Serum corticosterone level was much higher in both the stress-groups than the control groups. No neuronal death was found in all hippocampal subregions of the adult and aged gerbil after chronic restraint stress. GR immunoreactivity was decreased in both the adult and aged groups after repeated restraint stress; however, GR immunoreactivity in the adult-stress-group was decreased much more than that in the aged-stress-group. Iba-1 immunoreactive microglia were hypertrophied and activated in the adult group after repeated restraint stress; in the aged-stress-group, there was no any significant change in Iba-1 immunoreactive microglia. In brief, level of GR, not Iba-1, in the hippocampus was much decreased in the adult gerbil compared to the aged gerbil following chronic restraint stress.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Johnson EO, Kamilaris TC, Chrousos GP et al (1992) Mechanisms of stress: a dynamic overview of hormonal and behavioral homeostasis. Neurosci Biobehav Rev 16:115–130

    Article  PubMed  CAS  Google Scholar 

  2. McEwen BS (2000) The neurobiology of stress: from serendipity to clinical relevance. Brain Res 886:172–189

    Article  PubMed  CAS  Google Scholar 

  3. Korte SM (2001) Corticosteroids in relation to fear, anxiety and psychopathology. Neurosci Biobehav Rev 25:117–142

    Article  PubMed  CAS  Google Scholar 

  4. McEwen BS (1999) Stress and hippocampal plasticity. Annu Rev Neurosci 22:105–122

    Article  PubMed  CAS  Google Scholar 

  5. Blandino P Jr, Barnum CJ, Deak T (2006) The involvement of norepinephrine and microglia in hypothalamic and splenic IL-1beta responses to stress. J Neuroimmunol 173:87–95

    Article  PubMed  CAS  Google Scholar 

  6. Kwon MS, Seo YJ, Lee JK et al (2008) The repeated immobilization stress increases IL-1beta immunoreactivities in only neuron, but not astrocyte or microglia in hippocampal CA1 region, striatum and paraventricular nucleus. Neurosci Lett 430:258–263

    Article  PubMed  CAS  Google Scholar 

  7. Choi JH, Lee CH, Hwang IK et al (2007) Age-related changes in ionized calcium-binding adapter molecule 1 immunoreactivity and protein level in the gerbil hippocampal CA1 region. J Vet Med Sci 69:1131–1136

    Article  PubMed  CAS  Google Scholar 

  8. Kreutzberg GW (1996) Microglia: a sensor for pathological events in the CNS. Trends Neurosci 19:312–318

    Article  PubMed  CAS  Google Scholar 

  9. Ambrosini E, Aloisi F (2004) Chemokines and glial cells: a complex network in the central nervous system. Neurochem Res 29:1017–1038

    Article  PubMed  CAS  Google Scholar 

  10. Nair A, Bonneau RH (2006) Stress-induced elevation of glucocorticoids increases microglia proliferation through NMDA receptor activation. J Neuroimmunol 171:72–85

    Article  PubMed  CAS  Google Scholar 

  11. Romanova TP, Karpel GG, Brill GE et al (1994) Mechanism of disorders of the cerebral blood supply during stress in spontaneously hypertensive rats. Patol Fiziol Eksp Ter 3:5–8

    PubMed  Google Scholar 

  12. Singh LK, Pang X, Alexacos N et al (1999) Acute immobilization stress triggers skin mast cell degranulation via corticotropin releasing hormone, neurotensin, and substance P: A link to neurogenic skin disorders. Brain Behav Immun 13:225–239

    Article  PubMed  CAS  Google Scholar 

  13. Kim JJ, Diamond DM (2002) The stressed hippocampus, synaptic plasticity and lost memories. Nat Rev Neurosci 3:453–462

    Article  PubMed  CAS  Google Scholar 

  14. Kudo K, Wati H, Qiao C et al (2005) Age-related disturbance of memory and CREB phosphorylation in CA1 area of hippocampus of rats. Brain Res 1054:30–37

    Article  PubMed  CAS  Google Scholar 

  15. Mukaetova-Ladinska EB, Harrington CR, Roth M et al (1996) Alterations in tau protein metabolism during normal aging. Dementia 7:95–103

    PubMed  CAS  Google Scholar 

  16. Kristofikova Z, Stastny F, Bubenikova V et al (2004) Age- and sex-dependent laterality of rat hippocampal cholinergic system in relation to animal models of neurodevelopmental and neurodegenerative disorders. Neurochem Res 29:671–680

    Article  PubMed  Google Scholar 

  17. Sapolsky RM, Packan DR, Vale WW (1988) Glucocorticoid toxicity in the hippocampus: in vitro demonstration. Brain Res 453:367–371

    Article  PubMed  CAS  Google Scholar 

  18. Roozendaal B, Griffith QK, Buranday J et al (2003) The hippocampus mediates glucocorticoid-induced impairment of spatial memory retrieval: dependence on the basolateral amygdala. Proc Natl Acad Sci USA 100:1328–1333

    Article  PubMed  CAS  Google Scholar 

  19. Patel PD, Lopez JF, Lyons DM et al (2000) Glucocorticoid and mineralocorticoid receptor mRNA expression in squirrel monkey brain. J Psychiatr Res 34:383–392

    Article  PubMed  CAS  Google Scholar 

  20. Herman JP, Patel PD, Akil H et al (1989) Localization and regulation of glucocorticoid and mineralocorticoid receptor messenger RNAs in the hippocampal formation of the rat. Mol Endocrinol 3:1886–1894

    Article  PubMed  CAS  Google Scholar 

  21. Goodman Y, Bruce AJ, Cheng B et al (1996) Estrogens attenuate and corticosterone exacerbates excitotoxicity, oxidative injury, and amyloid beta-peptide toxicity in hippocampal neurons. J Neurochem 66:1836–1844

    Article  PubMed  CAS  Google Scholar 

  22. McCullers DL, Sullivan PG, Scheff SW et al (2002) Mifepristone protects CA1 hippocampal neurons following traumatic brain injury in rat. Neuroscience 109:219–230

    Article  PubMed  CAS  Google Scholar 

  23. Hwang IK, Yoo KY, Nam YS et al (2006) Mineralocorticoid and glucocorticoid receptor expressions in astrocytes and microglia in the gerbil hippocampal CA1 region after ischemic insult. Neurosci Res 54:319–327

    Article  PubMed  CAS  Google Scholar 

  24. Schmued LC, Hopkins KJ (2000) Fluoro-Jade B: a high affinity fluorescent marker for the localization of neuronal degeneration. Brain Res 874:123–130

    Article  PubMed  CAS  Google Scholar 

  25. Yu JT, Lee CH, Yoo KY et al (2010) Maintenance of anti-inflammatory cytokines and reduction of glial activation in the ischemic hippocampal CA1 region preconditioned with lipopolysaccharide. J Neurol Sci 296:69–78

    Article  PubMed  CAS  Google Scholar 

  26. Hwang IK, Yoo KY, Kim DW et al (2006) Ionized calcium-binding adapter molecule 1 immunoreactive cells change in the gerbil hippocampal CA1 region after ischemia/reperfusion. Neurochem Res 31:957–965

    Article  PubMed  CAS  Google Scholar 

  27. Cheal ML (1986) The gerbil: an unique model for research on aging. Exp Aging Res 12:3–21

    PubMed  CAS  Google Scholar 

  28. Morrison JH, Hof PR (1997) Life and death of neurons in the aging brain. Science 278:412–419

    Article  PubMed  CAS  Google Scholar 

  29. Hwang IK, Nam YS, Chung DW et al (2004) Changes in the expression of calbindin D-28k in the gerbil hippocampus following seizure. Neurochem Int 44:145–152

    Article  PubMed  CAS  Google Scholar 

  30. Buchanan JB, Sparkman NL, Chen J et al (2008) Cognitive and neuroinflammatory consequences of mild repeated stress are exacerbated in aged mice. Psychoneuroendocrinology 33:755–765

    Article  PubMed  CAS  Google Scholar 

  31. McIntosh LJ, Sapolsky RM (1996) Glucocorticoids increase the accumulation of reactive oxygen species and enhance adriamycin-induced toxicity in neuronal culture. Exp Neurol 141:201–206

    Article  PubMed  CAS  Google Scholar 

  32. Touyarot K, Sandi C (2002) Chronic restraint stress induces an isoform-specific regulation on the neural cell adhesion molecule in the hippocampus. Neural Plast 9:147–159

    Article  PubMed  CAS  Google Scholar 

  33. Kitraki E, Kremmyda O, Youlatos D et al (2004) Gender-dependent alterations in corticosteroid receptor status and spatial performance following 21 days of restraint stress. Neuroscience 125:47–55

    Article  PubMed  CAS  Google Scholar 

  34. Yun J, Koike H, Ibi D et al (2010) Chronic restraint stress impairs neurogenesis and hippocampus-dependent fear memory in mice: possible involvement of a brain-specific transcription factor Npas4. J Neurochem 114:1840–1851

    Article  PubMed  CAS  Google Scholar 

  35. Shoji H, Mizoguchi K (2010) Acute and repeated stress differentially regulates behavioral, endocrine, neural parameters relevant to emotional and stress response in young and aged rats. Behav Brain Res 211:169–177

    Article  PubMed  CAS  Google Scholar 

  36. Schwendt M, Jezova D (2000) Gene expression of two glutamate receptor subunits in response to repeated stress exposure in rat hippocampus. Cell Mol Neurobiol 20:319–329

    Article  PubMed  CAS  Google Scholar 

  37. Fontella FU, Siqueira IR, Vasconcellos AP et al (2005) Repeated restraint stress induces oxidative damage in rat hippocampus. Neurochem Res 30:105–111

    Article  PubMed  CAS  Google Scholar 

  38. Lee YJ, Choi B, Lee EH et al (2006) Immobilization stress induces cell death through production of reactive oxygen species in the mouse cerebral cortex. Neurosci Lett 392:27–31

    Article  PubMed  CAS  Google Scholar 

  39. Galea LA, McEwen BS, Tanapat P et al (1997) Sex differences in dendritic atrophy of CA3 pyramidal neurons in response to chronic restraint stress. Neuroscience 81:689–697

    Article  PubMed  CAS  Google Scholar 

  40. Sousa N, Lukoyanov NV, Madeira MD et al (2000) Reorganization of the morphology of hippocampal neurites and synapses after stress-induced damage correlates with behavioral improvement. Neuroscience 97:253–266

    Article  PubMed  CAS  Google Scholar 

  41. Venero C, Tilling T, Hermans-Borgmeyer I et al (2002) Chronic stress induces opposite changes in the mRNA expression of the cell adhesion molecules NCAM and L1. Neuroscience 115:1211–1219

    Article  PubMed  CAS  Google Scholar 

  42. Murphy EK, Spencer RL, Sipe KJ et al (2002) Decrements in nuclear glucocorticoid receptor (GR) protein levels and DNA binding in aged rat hippocampus. Endocrinology 143:1362–1370

    Article  PubMed  CAS  Google Scholar 

  43. Kitraki E, Kremmyda O, Youlatos D et al (2004) Spatial performance and corticosteroid receptor status in the 21 days restraint stress paradigm. Ann N Y Acad Sci 1018:323–327

    Article  PubMed  CAS  Google Scholar 

  44. Wright RL, Lightner EN, Harman JS et al (2006) Attenuating corticosterone levels on the day of memory assessment prevents chronic stress-induced impairments in spatial memory. Eur J Neurosci 24:595–605

    Article  PubMed  Google Scholar 

  45. Zhou J, Li L, Tang S et al (2008) Effects of serotonin depletion on the hippocampal GR/MR and BDNF expression during the stress adaptation. Behav Brain Res 195:129–138

    Article  PubMed  CAS  Google Scholar 

  46. Smith MA, Cizza G (1996) Stress-induced changes in brain-derived neurotrophic factor expression are attenuated in aged Fischer 344/N rats. Neurobiol Aging 17:859–864

    Article  PubMed  CAS  Google Scholar 

  47. Sugama S (2009) Stress-induced microglial activation may facilitate the progression of neurodegenerative disorders. Med Hypotheses 73:1031–1034

    Article  PubMed  CAS  Google Scholar 

  48. Tanaka J, Fujita H, Matsuda S et al (1997) Glucocorticoid- and mineralocorticoid receptors in microglial cells: the two receptors mediate differential effects of corticosteroids. Glia 20:23–37

    Article  PubMed  CAS  Google Scholar 

  49. Lee CH, Yoo KY, Choi JH et al (2010) Neuronal damage is much delayed and microgliosis is more severe in the aged hippocampus induced by transient cerebral ischemia compared to the adult hippocampus. J Neurol Sci 294:1–6

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Mr. Seung Uk Lee and Ms. Hyun Sook Kim for their technical help. This study was supported by the Regional Core Research Program funded by the Korea Ministry of Education, Science and Technology (Medical and Bio-material Research Center) and by a grant (2010K000823) from Brain Research Center of the twenty-firstst Century Frontier Research Program funded by the Ministry of Education, Science and Technology, the Republic of Korea.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Choong Hyun Lee or Moo-Ho Won.

Additional information

Joon Ha Park and Ki-Yeon Yoo contributed equally to this article.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Park, J.H., Yoo, KY., Lee, C.H. et al. Comparison of Glucocorticoid Receptor and Ionized Calcium-Binding Adapter Molecule 1 Immunoreactivity in the Adult and Aged Gerbil Hippocampus Following Repeated Restraint Stress. Neurochem Res 36, 1037–1045 (2011). https://doi.org/10.1007/s11064-011-0444-z

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-011-0444-z

Keywords

Navigation