NeuroMolecular Medicine

, Volume 12, Issue 1, pp 56–70 | Cite as

Adverse Stress, Hippocampal Networks, and Alzheimer’s Disease

  • Sarah M. RothmanEmail author
  • Mark P. Mattson
Review Paper


Recent clinical data have implicated chronic adverse stress as a potential risk factor in the development of Alzheimer’s disease (AD) and data also suggest that normal, physiological stress responses may be impaired in AD. It is possible that pathology associated with AD causes aberrant responses to chronic stress, due to potential alterations in the hypothalamic–pituitary–adrenal (HPA) axis. Recent study in rodent models of AD suggests that chronic adverse stress exacerbates the cognitive deficits and hippocampal pathology that are present in the AD brain. This review summarizes recent findings obtained in experimental AD models regarding the influence of chronic adverse stress on the underlying cellular and molecular disease processes including the potential role of glucocorticoids. Emerging findings suggest that both AD and chronic adverse stress affect hippocampal neural networks in a similar fashion. We describe alterations in hippocampal plasticity, which occur in both chronic stress and AD including dendritic remodeling, neurogenesis, and long-term potentiation. Finally, we outline potential roles for oxidative stress and neurotrophic factor signaling as the key determinants of the impact of chronic stress on the plasticity of neural networks and AD pathogenesis.


Alzheimer’s disease Chronic stress Glucocorticoids Hippocampal plasticity 



This research was supported entirely by the Intramural Research Program of the NIH, National Institute on Aging.


  1. Aisa, B., Elizalde, N., Tordera, R., Lasheras, B., Del Río, J., & Ramírez, M. J. (2009). Effects of neonatal stress on markers of synaptic plasticity in the hippocampus: Implications for spatial memory. Hippocampus (in press).Google Scholar
  2. Aleisa, A. M., Alzoubi, K. H., Gerges, N. Z., & Alkadhi, K. A. (2006). Chronic psychosocial stress-induced impairment of hippocampal LTP: Possible role of BDNF. Neurobiology of Diseases, 22, 453–462.CrossRefGoogle Scholar
  3. Alfarez, D. N., Joëls, M., & Krugers, H. J. (2003). Chronic unpredictable stress impairs long-term potentiation in rat hippocampal CA1 area and dentate gyrus in vitro. European Journal of Neuroscience, 17, 1928–1934.PubMedCrossRefGoogle Scholar
  4. Alfarez, D. N., Weigert, O., Joëls, M., & Krugers, H. J. (2002). Corticosterone and stress reduce synaptic potentiation in mouse hippocampal slices with mild stimulation. Neuroscience, 115, 1119–1126.PubMedCrossRefGoogle Scholar
  5. Atif, F., Yousuf, S., & Agrawal, S. K. (2008). Restraint stress-induced oxidative damage and its amelioration with selenium. European Journal of Pharmacology, 600, 59–63.PubMedCrossRefGoogle Scholar
  6. Begley, J. G., Duan, W., Chan, S., Duff, K., & Mattson, M. P. (1999). Altered calcium homeostasis and mitochondrial dysfunction in cortical synaptic compartments of presenilin-1 mutant mice. Journal of Neurochemistry, 72, 1030–1039.PubMedCrossRefGoogle Scholar
  7. Bobinski, M., de Leon, M. J., Tarnawski, M., Wegiel, J., Reisberg, B., Miller, D. C., et al. (1998). Neuronal and volume loss in CA1 of the hippocampal formation uniquely predicts duration and severity of Alzheimer disease. Brain Research, 805, 267–269.PubMedCrossRefGoogle Scholar
  8. Bohringer, A., Schwabe, L., Richter, S., & Schachinger, H. (2008). Intranasal insulin attenuates the hypothalamic-pituitary-adrenal axis response to psychosocial stress. Psychoneuroendocrinology, 33, 1394–1400.PubMedCrossRefGoogle Scholar
  9. Breyhan, H., Wirths, O., Duan, K., Marcello, A., Rettig, J., & Bayer, T. A. (2009). APP/PS1KI bigenic mice develop early synaptic deficits and hippocampus atrophy. Acta Neuropathologica, 117, 677–685.PubMedCrossRefGoogle Scholar
  10. Bruce-Keller, A. J., Umberger, G., McFall, R., & Mattson, M. P. (1999). Food restriction reduces brain damage and improves behavioral outcome following excitotoxic and metabolic insults. Annals of Neurology, 45, 8–15.PubMedCrossRefGoogle Scholar
  11. Bubber, P., Haroutunian, V., Fisch, G., Blass, J. P., & Gibson, G. E. (2005). Mitochondrial abnormalities in Alzheimer brain: Mechanistic implications. Annals of Neurology, 57, 695–703.PubMedCrossRefGoogle Scholar
  12. Butterfield, D. A., & Boyd-Kimball, D. (2004). Amyloid beta-peptide(1-42) contributes to the oxidative stress and neurodegeneration found in Alzheimer disease brain. Brain Pathology, 14, 426–432.PubMedGoogle Scholar
  13. Butterfield, D. A., Drake, J., Pocernich, C., & Castegna, A. (2001). Evidence of oxidative damage in Alzheimer’s disease brain: Central role for amyloid beta-peptide. Trends in Molecular Medicine, 7, 548–554.PubMedCrossRefGoogle Scholar
  14. Buttini, M., Masliah, E., Barbour, R., Grajeda, H., Motter, R., Johnson-Wood, K., et al. (2005). Beta-amyloid immunotherapy prevents synaptic degeneration in a mouse model of Alzheimer’s disease. Journal of Neuroscience, 25, 9096–9101.PubMedCrossRefGoogle Scholar
  15. Cameron, H. A., Woolley, C. S., McEwen, B. S., & Gould, E. (1993). Differentiation of newly born neurons and glia in the dentate gyrus of the adult rat. Neuroscience, 56, 337–344.PubMedCrossRefGoogle Scholar
  16. Casas, C., Sergeant, N., Itier, J. M., Blanchard, V., Wirths, O., van der Kolk, N., et al. (2004). Massive CA1/2 neuronal loss with intraneuronal and N-terminal truncated Abeta42 accumulation in a novel Alzheimer transgenic model. American Journal of Pathology, 165, 1289–1300.PubMedGoogle Scholar
  17. Catania, C., Sotiropoulos, I., Silva, R., Onofri, C., Breen, K. C., Sousa, N., et al. (2009). The amyloidogenic potential and behavioral correlates of stress. Molecular Psychiatry, 14, 95–105.PubMedCrossRefGoogle Scholar
  18. Cerqueira, J. J., Mailliet, F., Almeida, O. F., Jay, T. M., & Sousa, N. (2007). The prefrontal cortex as a key target of the maladaptive response to stress. Journal of Neuroscience, 27, 2781–2787.PubMedCrossRefGoogle Scholar
  19. Connor, B., Young, D., Yan, Q., Faull, R. L., Synek, B., & Dragunow, M. (1997). Brain-derived neurotrophic factor is reduced in Alzheimer’s disease. Brain Research. Molecular Brain Research, 49, 71–81.PubMedCrossRefGoogle Scholar
  20. Conrad, C. D., Lupien, S. J., & McEwen, B. S. (1999). Support for a bimodal role for type II adrenal steroid receptors in spatial memory. Neurobiology of Learning and Memory, 72, 39–46.PubMedCrossRefGoogle Scholar
  21. Craft, S. (2009). The role of metabolic disorders in Alzheimer disease and vascular dementia: Two roads converged. Archives of Neurology, 66, 300–305.PubMedCrossRefGoogle Scholar
  22. Csernansky, J. G., Dong, H., Fagan, A. M., Wang, L., Xiong, C., Holtzman, D. M., et al. (2006). Plasma cortisol and progression of dementia in subjects with Alzheimer-type dementia. American Journal of Psychiatry, 163, 2164–2169.PubMedCrossRefGoogle Scholar
  23. Czéh, B., Welt, T., Fischer, A. K., Erhardt, A., Schmitt, W., Müller, M. B., et al. (2003). Chronic psychosocial stress and concomitant repetitive transcranial magnetic stimulation: Effects on stress hormone levels and adult hippocampal neurogenesis. Biological Psychiatry, 52, 1057–1065.CrossRefGoogle Scholar
  24. Dallman, M. F., Akana, S. F., Strack, A. M., Hanson, E. S., & Sebastian, R. J. (1995). The neural network that regulates energy balance is responsive to glucocorticoids and insulin and also regulates HPA axis responsivity at a site proximal to CRF neurons. Annals of the New York Academy of Sciences, 771, 730–742.PubMedCrossRefGoogle Scholar
  25. David, D. J., Samuels, B. A., Rainer, Q., Wang, J. W., Marsteller, D., Mendez, I., et al. (2009). Neurogenesis-dependent and -independent effects of fluoxetine in an animal model of anxiety/depression. Neuron, 62, 479–493.PubMedCrossRefGoogle Scholar
  26. Davis, K. L., Davis, B. M., Greenwald, B. S., Mohs, R. C., Mathe, A. A., Johns, C. A., et al. (1986). Cortisol and Alzheimer’s disease, I: Basal studies. The American Journal of Psychiatry, 143, 300–305.PubMedGoogle Scholar
  27. de Kloet, E. R., & Derijk, R. (2004). Signaling pathways in brain involved in predisposition and pathogenesis of stress-related disease: Genetic and kinetic factors affecting the MR/GR balance. Annals of the New York Academy of Sciences, 1032, 14–34.PubMedCrossRefGoogle Scholar
  28. de Kloet, E. R., Oitzl, M. S., & Joëls, M. (1999). Stress and cognition: Are corticosteroids good or bad guys? Trends in Neurosciences, 22, 422–426.PubMedCrossRefGoogle Scholar
  29. Diamond, D. M., Bennett, M. C., Fleshner, M., & Rose, G. M. (1992). Inverted-U relationship between the level of peripheral corticosterone and the magnitude of hippocampal primed burst potentiation. Hippocampus, 2, 421–430.PubMedCrossRefGoogle Scholar
  30. Dong, H., Goico, B., Martin, M., Csernansky, C. A., Bertchume, A., & Csernansky, J. G. (2004). Modulation of hippocampal cell proliferation, memory, and amyloid plaque deposition in APPsw (Tg2576) mutant mice by isolation stress. Neuroscience, 127, 601–609.PubMedCrossRefGoogle Scholar
  31. Dong, H., Yuede, C. M., Yoo, H. S., Martin, M. V., Deal, C., Mace, A. G., et al. (2008). Corticosterone and related receptor expression are associated with increased β-amyloid plaques in isolated Tg2576 mice. Neuroscience, 155, 154–163.PubMedCrossRefGoogle Scholar
  32. Donohue, H. S., Gabbott, P. L., Davies, H. A., Rodríguez, J. J., Cordero, M. I., Sandi, C., et al. (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.PubMedCrossRefGoogle Scholar
  33. Droste, S. K., Collins. A., Lightman, S. L., Linthorst. A. C., & Reul, J. M. (2009). Distinct, time-dependent effects of voluntary exercise on circadian and ultradian rhythms and stress responses of free corticosterone in the rat hippocampus. Endocrinology, 150(9), 4170–4179.Google Scholar
  34. Du, J., Wang, Y., Hunter, R., Wei, Y., Blumenthal, R., Falke, C., et al. (2009). Dynamic regulation of mitochondrial function by glucocorticoids. Proceedings of the National Academy of Sciences of the United States of America, 106, 3543–3548.PubMedCrossRefGoogle Scholar
  35. Eriksson, P. S., Perfilieva, E., Björk-Eriksson, T., Alborn, A. M., Nordborg, C., Peterson, D. A., et al. (1998). Neurogenesis in the adult human hippocampus. Nature Medicine, 4, 1313–1317.PubMedCrossRefGoogle Scholar
  36. Friedland, R. P., Jagust, W. J., Huesman, R. H., Koss, E., Knittel, B., Mathis, C. A., et al. (1989). Regional cerebral glucose transport and utilization in Alzheimer’s disease. Neurology, 39, 1427–1434.PubMedGoogle Scholar
  37. Fu, J. H., Xie, S. R., Kong, S. J., Wang, Y., Wei, W., Shan, Y., et al. (2009). The combination of a high-fat diet and chronic stress aggravates insulin resistance in Wistar male rats. Experimental and Clinical Endocrinology & Diabetes, 117(7), 354–360.Google Scholar
  38. Fuchs, E., & Flugge, G. (1998). Stress, glucocorticoids and structural plasticity of the hippocampus. Neuroscience and Biobehavioral Reviews, 23, 295–300.PubMedCrossRefGoogle Scholar
  39. Fuchs, E., Flugge, G., & Czeh, B. (2006). Remodeling of neural networks by stress. Frontiers Bioscience, 11, 2746–2758.CrossRefGoogle Scholar
  40. Fumagalli, F., Di Pasquale, L., Caffino, L., Racagni, G., & Riva, M. A. (2008). Stress and cocaine interact to modulate basic fibroblast growth factor (FGF-2) expression in rat brain. Psychopharmacology, 196, 357–364.PubMedCrossRefGoogle Scholar
  41. Gómez-Pinilla, F., Dao, L., & So, V. (1997). Physical exercise induces FGF-2 and its mRNA in the hippocampus. Brain Research, 764, 1–8.PubMedCrossRefGoogle Scholar
  42. Gomez-Pinilla, F., Vaynman, S., & Ying, Z. (2008). Brain-derived neurotrophic factor functions as a metabotrophin to mediate the effects of exercise on cognition. European Journal of Neuroscience, 28, 2278–2287.PubMedCrossRefGoogle Scholar
  43. Gong, Y., Chang, L., Viola, K. L., Lacor, P. N., Lambert, M. P., Finch, C. E., et al. (2003). Alzheimer’s disease-affected brain: presence of oligomeric A beta ligands (ADDLs) suggests a molecular basis for reversible memory loss. Proceedings of the National Academy of Sciences of the United States of America, 100, 10417–10422.PubMedCrossRefGoogle Scholar
  44. Goodman, Y., Bruce, A. J., Cheng, B., & Mattson, M. P. (1996). Estrogens attenuate and corticosterone exacerbates excitotoxicity, oxidative injury, and amyloid beta-peptide toxicity in hippocampal neurons. Journal of Neurochemistry, 66, 1836–1844.PubMedCrossRefGoogle Scholar
  45. Goodman, Y., & Mattson, M. P. (1994). Secreted forms of beta-amyloid precursor protein protect hippocampal neurons against amyloid beta-peptide-induced oxidative injury. Experimental Neurology, 128, 1–12.PubMedCrossRefGoogle Scholar
  46. Gould, E., McEwen, B. S., Tanapat, P., Galea, L. A., & Fuchs, E. (1997). Neurogenesis in the dentate gyrus of the adult tree shrew is regulated by psychosocial stress and NMDA receptor activation. Journal of Neuroscience, 17, 2492–2498.PubMedGoogle Scholar
  47. Graves, L. A., Heller, E. A., Pack, A. I., & Abel, T. (2003). Sleep deprivation selectively impairs memory consolidation for contextual fear conditioning. Learning and Memory, 10, 168–176.PubMedCrossRefGoogle Scholar
  48. Green, K. N., Billings, L. M., Roozendaal, B., McGaugh, J. L., & LaFerla, F. M. (2006). Glucocorticoids increase amyloid-β and tau pathology in a mouse model of Alzheimer’s disease. Journal of Neuroscience, 26, 9047–9056.PubMedCrossRefGoogle Scholar
  49. Hajszan, T., Dow, A., Warner-Schmidt, J. L., Szigeti-Buck, K., Sallam, N. L., Parducz, A., et al. (2009). Remodeling of hippocampal spine synapses in the rat learned helplessness model of depression. Biological Psychiatry, 65, 392–400.PubMedCrossRefGoogle Scholar
  50. Haughey, N. J., Nath, A., Chan, S. L., Borchard, A. C., Rao, M. S., & Mattson, M. P. (2002). Disruption of neurogenesis by amyloid beta-peptide, and perturbed neural progenitor cell homeostasis, in models of Alzheimer’s disease. Journal of Neurochemistry, 83, 1509–1524.PubMedCrossRefGoogle Scholar
  51. Hauptmann, S., Scherping, I., Dröse, S., Brandt, U., Schulz, K. L., Jendrach, M., et al. (2008). Mitochondrial dysfunction: An early event in Alzheimer pathology accumulates with age in AD transgenic mice. Neurobiology of Aging, 30(10), 1574–1586.Google Scholar
  52. Henneman, W. J., Sluimer, J. D., Barnes, J., van der Flier, W. M., Sluimer, I. C., Fox, N. C., et al. (2009). Hippocampal atrophy rates in Alzheimer disease: Added value over whole brain volume measures. Neurology, 72, 999–1007.PubMedCrossRefGoogle Scholar
  53. Hensley, K., Carney, J. M., Mattson, M. P., Aksenova, M., Harris, M., Wu, J. F., et al. (1994). A model for beta-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease. Proceedings of the National Academy of Sciences of the United States of America, 91, 3270–3274.PubMedCrossRefGoogle Scholar
  54. Herman, J. P., Schäfer, M. K., Young, E. A., Thompson, R., Douglass, J., Akil, H., et al. (1989). Evidence for hippocampal regulation of neuroendocrine neurons of the hypothalamo-pituitary-adrenocortical axis. Journal of Neuroscience, 9, 3072–3082.PubMedGoogle Scholar
  55. Hock, C., Heese, K., Hulette, C., Rosenberg, C., & Otten, U. (2000). Region-specific neurotrophin imbalances in Alzheimer disease: Decreased levels of brain-derived neurotrophic factor and increased levels of nerve growth factor in hippocampus and cortical areas. Archives of Neurology, 57, 846–851.PubMedCrossRefGoogle Scholar
  56. Holderbach, R., Clark, K., Moreau, J. L., Bischofberger, J., & Normann, C. (2007). Enhanced long-term synaptic depression in an animal model of depression. Biological Psychiatry, 62, 92–100.PubMedCrossRefGoogle Scholar
  57. Horner, H. C., Packan, D. R., & Sapolsky, R. M. (1990). Glucocorticoids inhibit glucose transport in cultured hippocampal neurons and glia. Neuroendocrinology, 52, 57–64.PubMedCrossRefGoogle Scholar
  58. Ibi, D., Takuma, K., Koike, H., Mizoguchi, H., Tsuritani, K., Kuwahara, Y., et al. (2008). Social isolation rearing-induced impairment of the hippocampal neurogenesis is associated with deficits in spatial memory and emotion-related behaviors in juvenile mice. Journal of Neurochemistry, 105, 921–932.PubMedCrossRefGoogle Scholar
  59. Imayoshi, I., Sakamoto, M., Ohtsuka, T., & Kageyama, R. (2009). Continuous neurogenesis in the adult brain. Development Growth and Differentiation, 51, 379–386.CrossRefGoogle Scholar
  60. Irie, K., Murakami, K., Masuda, Y., Morimoto, A., Ohigashi, H., Hara, H., et al. (2007). The toxic conformation of the 42-residue amyloid beta peptide and its relevance to oxidative stress in Alzheimer’s disease. Mini Reviews in Medicinal Chemistry, 7, 1001–1008.PubMedCrossRefGoogle Scholar
  61. Jacobsen, J. S., Wu, C. C., Redwine, J. M., Comery, T. A., Arias, R., Bowlby, M., et al. (2006). Early-onset behavioral and synaptic deficits in a mouse model of Alzheimer’s disease. Proceedings of the National Academy of Sciences of the United States of America, 103, 5161–5166.PubMedCrossRefGoogle Scholar
  62. Jacobson, L., & Sapolsky, R. (1991). The role of the hippocampus in feedback regulation of the hypothalamic-pituitary-adrenocortical axis. Endocrine Reviews, 12, 118–134.PubMedCrossRefGoogle Scholar
  63. Jeong, Y. H., Park, C. H., Yoo, J., Shin, K. J., Ahn, S. M., Kim, H. S., et al. (2006). Chronic stress accelerates learning and memory impairments and increases amyloid deposition in APPV7171-CT100 transgenic mice, an Alzheimer’s disease model. The FASEB Journal, 20, 729–731.PubMedGoogle Scholar
  64. Jin, K., Peel, A. L., Mao, X. O., Xie, L., Cottrell, B. A., Henshall, D. C., et al. (2004). Increased hippocampal neurogenesis in Alzheimer’s disease. Proceedings of the National Academy of Sciences of the United States of America, 101, 343–347.PubMedCrossRefGoogle Scholar
  65. Joëls, M., & Krugers, H. J. (2007). LTP after stress: Up or down? Neural Plasticity, 2007, 93202.PubMedCrossRefGoogle Scholar
  66. Johnson, N. A., Jahng, G. H., Weiner, M. W., Miller, B. L., Chui, H. C., Jagust, W. J., et al. (2005). Pattern of cerebral hypoperfusion in Alzheimer disease and mild cognitive impairment measured with arterial spin-labeling MR imaging: Initial experience. Radiology, 234, 851–859.PubMedCrossRefGoogle Scholar
  67. Keller, J. N., Mark, R. J., Bruce, A. J., Blanc, E., Rothstein, J. D., Uchida, K., et al. (1997). 4-Hydroxynonenal, an aldehydic product of membrane lipid peroxidation, impairs glutamate transport and mitochondrial function in synaptosomes. Neuroscience, 80, 685–696.PubMedCrossRefGoogle Scholar
  68. Kempermann, G., Gast, D., & Gage, F. H. (2002). Neuroplasticity in old age: sustained fivefold induction of hippocampal neurogenesis by long-term environmental enrichment. Annals of Neurology, 52, 135–143.PubMedCrossRefGoogle Scholar
  69. Krugers, H. J., Douma, B. R., Andringa, G., Bohus, B., Korf, J., & Luiten, P. G. (1997). Exposure to chronic psychosocial stress and corticosterone in the rat: Effects on spatial discrimination learning and hippocampal protein kinase Cgamma immunoreactivity. Hippocampus, 7, 427–436.PubMedCrossRefGoogle Scholar
  70. Kulstad, J. J., McMillan, P. J., Leverenz, J. B., Cook, D. G., Green, P. S., Peskind, E. R., et al. (2005). Effects of chronic glucocorticoid administration on insulin-degrading enzyme and amyloid-beta peptide in the aged macaque. Journal of Neuropathology and Experimental Neurology, 64, 139–146.PubMedGoogle Scholar
  71. Lacor, P. N., Buniel, M. C., Chang, L., Fernandez, S. J., Gong, Y., Viola, K. L., et al. (2004). Synaptic targeting by Alzheimer’s-related amyloid beta oligomers. Journal of Neuroscience, 24, 10191–10200.PubMedCrossRefGoogle Scholar
  72. Lee, J., Duan, W., & Mattson, M. P. (2002a). Evidence that brain-derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice. Journal of Neurochemistry, 82, 1367–1375.PubMedCrossRefGoogle Scholar
  73. Lee, J., Herman, J. P., & Mattson, M. P. (2000). Dietary restriction selectively decreases glucocorticoid receptor expression in the hippocampus and cerebral cortex of rats. Experimental Neurology, 166, 435–441.PubMedCrossRefGoogle Scholar
  74. Lee, K. W., Kim, J. B., Seo, J. S., Kim, T. K., Im, J. Y., Baek, I. S., et al. (2009). Behavioral stress accelerates plaque pathogenesis in the brain of Tg2576 mice via generation of metabolic oxidative stress. Journal of Neurochemistry, 108, 165–175.PubMedCrossRefGoogle Scholar
  75. Lee, J., Seroogy, K. B., & Mattson, M. P. (2002b). Dietary restriction enhances neurotrophin expression and neurogenesis in the hippocampus of adult mice. Journal of Neurochemistry, 80, 539–547.PubMedCrossRefGoogle Scholar
  76. Li, Y., Perry, T., Kindy, M. S., Harvey, B. K., Tweedie, D., Holloway, H. W., et al. (2009). GLP-1 receptor stimulation preserves primary cortical and dopaminergic neurons in cellular and rodent models of stroke and Parkinsonism. Proceedings of the National Academy of Sciences of the United States of America, 106, 1285–1290.PubMedCrossRefGoogle Scholar
  77. Li, S., Wang, C., Wang, W., Dong, H., Hou, P., & Tang, Y. (2008). Chronic mild stress impairs cognition in mice: From brain homeostasis to behavior. Life Sciences, 82, 934–942.PubMedCrossRefGoogle Scholar
  78. Liu, L., Orozco, I. J., Planel, E., Wen, Y., Bretteville, A., Krishnamurthy, P., et al. (2008). A transgenic rat that develops Alzheimer’s disease-like amyloid pathology, deficits in synaptic plasticity and cognitive impairment. Neurobiology of Diseases, 31, 46–57.CrossRefGoogle Scholar
  79. Löckenhoff, C. E., Terracciano, A., Patriciu, N. S., Eaton, W. W., & Costa, P. T., Jr. (2009). Self-reported extremely adverse life events and longitudinal changes in five-factor model personality traits in an urban sample. Journal of Traumatic Stress, 22, 53–59.PubMedCrossRefGoogle Scholar
  80. Lucassen, P. J., Heine, V. M., Muller, M. B., van der Beek, E. M., Wiegant, V. M., De Kloet, E. R., et al. (2006). Stress, depression and hippocampal apoptosis. CNS & Neurological Disorders Drug Targets, 5, 531–546.CrossRefGoogle Scholar
  81. Magariños, A. M., McEwen, B. S., Flügge, G., & Fuchs, E. (1996). Chronic psychosocial stress causes apical dendritic atrophy of hippocampal CA3 pyramidal neurons in subordinate tree shrews. Journal of Neuroscience, 16, 3534–3540.PubMedGoogle Scholar
  82. Magariños, A. M., Orchinik, M., & McEwen, B. S. (1998). Morphological changes in the hippocampal CA3 region induced by non-invasive glucocorticoid administration: A paradox. Brain Research, 809, 314–318.PubMedCrossRefGoogle Scholar
  83. Malberg, J. E., & Duman, R. S. (2003). Cell proliferation in adult hippocampus is decreased by inescapable stress: Reversal by fluoxetine treatment. Neuropsychopharmacology, 28, 1562–1571.PubMedCrossRefGoogle Scholar
  84. Marini, A. M., Jiang, X., Wu, X., Pan, H., Guo, Z., Mattson, M. P., et al. (2007). Preconditioning and neurotrophins: A model for brain adaptation to seizures, ischemia and other stressful stimuli. Amino Acids, 32, 299–304.PubMedCrossRefGoogle Scholar
  85. Mark, R. J., Pang, Z., Geddes, J. W., Uchida, K., & Mattson, M. P. (1997). Amyloid beta-peptide impairs glucose transport in hippocampal and cortical neurons: Involvement of membrane lipid peroxidation. Journal of Neuroscience, 17, 1046–1054.PubMedGoogle Scholar
  86. Martin, S. J., & Clark, R. E. (2007). The rodent hippocampus and spatial memory: From synapses to systems. Cellular and Molecular Life Sciences, 64, 401–431.PubMedCrossRefGoogle Scholar
  87. Martin, B., Golden, E., Carlson, O. D., Pistell, P., Zhou, J., Kim, W., et al. (2009). Exendin-4 improves glycemic control, ameliorates brain and pancreatic pathologies, and extends survival in a mouse model of Huntington’s disease. Diabetes, 58, 318–328.PubMedCrossRefGoogle Scholar
  88. Matsuoka, Y., Picciano, M., La Francois, J., & Duff, K. (2001). Fibrillar beta-amyloid evokes oxidative damage in a transgenic mouse model of Alzheimer’s disease. Neuroscience, 104, 609–613.PubMedCrossRefGoogle Scholar
  89. Mattson, M. P. (2004). Pathways towards and away from Alzheimer’s disease. Nature, 430, 631–639.PubMedCrossRefGoogle Scholar
  90. Mattson, M. P. (2008). Awareness of hormesis will enhance future research in basic and applied neuroscience. Critical Reviews in Toxicology, 38, 633–639.PubMedCrossRefGoogle Scholar
  91. Mattson, M. P., Duan, W., Wan, R., & Guo, Z. (2004). Prophylactic activation of neuroprotective stress response pathways by dietary and behavioral manipulations. NeuroRx, 1, 111–116.PubMedCrossRefGoogle Scholar
  92. Mattson, M. P., Gleichmann, M., & Cheng, A. (2008). Mitochondria in neuroplasticity and neurological disorders. Neuron, 60, 748–766.PubMedCrossRefGoogle Scholar
  93. McEwen, B. S. (2001). Plasticity of the hippocampus: Adaptation to chronic stress and allostatic load. Annals of the New York Academy of Sciences, 933, 265–277.PubMedGoogle Scholar
  94. McEwen, B. S. (2006). Protective and damaging effects of stress mediators: Central role of the brain. Dialogues in Clinical Neuroscience, 8, 367–381.PubMedGoogle Scholar
  95. Mejia, S., Giraldo, M., Pineda, D., Ardila, A., & Lopera, F. (2003). Nongenetic factors as modifiers of the age of onset of familial alzheimer’s disease. International Psychogeriatrics, 15, 337–349.PubMedCrossRefGoogle Scholar
  96. Mowla, A., Mosavinasab, M., & Pani, A. (2007). Does fluoxetine have any effect on the cognition of patients with mild cognitive impairment? A double-blind, placebo-controlled, clinical trial. Journal of Clinical Psychopharmacology, 27, 67–70.PubMedCrossRefGoogle Scholar
  97. Munck, A., & Guyre, P. M. (1986). Glucocorticoid physiology, pharmacology and stress. Advances in Experimental Medicine and Biology, 196, 81–96.PubMedGoogle Scholar
  98. Nagahara, A. H., Merrill, D. A., Coppola, G., Tsukada, S., Schroder, B. E., Shaked, G. M., et al. (2009). Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer’s disease. Nature Medicine, 15, 331–337.PubMedCrossRefGoogle Scholar
  99. Nakajo, Y., Miyamoto, S., Nakano, Y., Xue, J. H., Hori, T., & Yanamoto, H. (2008). Genetic increase in brain-derived neurotrophic factor levels enhances learning and memory. Brain Research, 1241, 103–109.PubMedCrossRefGoogle Scholar
  100. Nelson, D. H. (1972). Regulation of glucocorticoid release. American Journal of Medicine, 53, 590–594.PubMedCrossRefGoogle Scholar
  101. Nelson, R. L., Guo, Z., Halagappa, V. M., Pearson, M., Gray, A. J., Matsuoka, Y., et al. (2007). Prophylactic treatment with paroxetine ameliorates behavioral deficits and retards the development of amyloid and tau pathologies in 3xTgAD mice. Experimental Neurology, 205, 166–176.PubMedCrossRefGoogle Scholar
  102. Nishi, M., Usuku, T., Itose, M., Fujikawa, K., Hosokawa, K., Matsuda, K. I., et al. (2007). Direct visualization of glucocorticoid receptor positive cells in the hippocampal regions using green fluorescent protein transgenic mice. Neuroscience, 146, 1555–1560.PubMedCrossRefGoogle Scholar
  103. Nuntagij, P., Oddo, S., LaFerla, F. M., Kotchabhakdi, N., Ottersen, O. P., & Torp, R. (2009). Amyloid deposits show complexity and intimate spatial relationship with dendrosomatic plasma membranes: an electron microscopic 3D reconstruction analysis in 3xTg-AD mice and aged canines. Journal of Alzheimer’s Disease, 16, 315–323.PubMedGoogle Scholar
  104. Pajović, S. B., Pejić, S., Stojiljković, V., Gavrilović, L., Dronjak, S., & Kanazir, D. T. (2006). Alterations in hippocampal antioxidant enzyme activities and sympatho-adrenomedullary system of rats in response to different stress models. Physiological Research, 55, 453–460.PubMedGoogle Scholar
  105. Pan, J. W., & Takahashi, K. (2007). Cerebral energetic effects of creatine supplementation in humans. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, 292, R1745–R1750.PubMedGoogle Scholar
  106. Park, C. R., Campbell, A. M., & Diamond, D. M. (2001). Chronic psychosocial stress impairs learning and memory and increases sensitivity to yohimbine in adult rats. Biological Psychiatry, 50, 994–1004.PubMedCrossRefGoogle Scholar
  107. Patel, N. V., & Finch, C. E. (2002). The glucocorticoid paradox of caloric restriction in slowing brain aging. Neurobiology of Aging, 23, 707–717.PubMedCrossRefGoogle Scholar
  108. Patel, P. D., Katz, M., Karssen, A. M., & Lyons, D. M. (2008). Stress-induced changes in corticosteroid receptor expression in primate hippocampus and prefrontal cortex. Psychoneuroendocrinology, 33, 360–367.PubMedCrossRefGoogle Scholar
  109. Pavlides, C., Nivón, L. G., & McEwen, B. S. (2002). Effects of chronic stress on hippocampal long-term potentiation. Hippocampus, 12, 245–257.PubMedCrossRefGoogle Scholar
  110. Pedersen, W. A., Culmsee, C., Ziegler, D., Herman, J. P., & Mattson, M. P. (1999). Aberrant stress response associated with severe hypoglycemia in a transgenic mouse model of Alzheimer’s disease. Journal of Molecular Neuroscience, 13, 159–165.PubMedCrossRefGoogle Scholar
  111. Pedersen, W. A., McMillan, P. J., Kulstad, J. J., Leverenz, J. B., Craft, S., & Haynatzki, G. R. (2006). Rosiglitazone attenuates learning and memory deficits in Tg2576 Alzheimer mice. Experimental Neurology, 199, 265–273.PubMedCrossRefGoogle Scholar
  112. Perneczky, R., Hartmann, J., Grimmer, T., Drzezga, A., & Kurz, A. (2007). Cerebral metabolic correlates of the clinical dementia rating scale in mild cognitive impairment. Journal of Geriatric Psychiatry and Neurology, 20, 84–88.PubMedCrossRefGoogle Scholar
  113. Pietropaolo, S., Sun, Y., Li, R., Brana, C., Feldon, J., & Yee, B. K. (2009). Limited impact of social isolation on Alzheimer-like symptoms in a triple transgenic mouse model. Behavioral Neuroscience, 123, 181–195.PubMedCrossRefGoogle Scholar
  114. Radák, Z., Kaneko, T., Tahara, S., Nakamoto, H., Pucsok, J., Sasvári, M., et al. (2001). Regular exercise improves cognitive function and decreases oxidative damage in rat brain. Neurochemistry International, 38, 17–23.PubMedCrossRefGoogle Scholar
  115. Rasmuson, S., Andrew, R., Näsman, B., Seckl, J. R., Walker, B. R., & Olsson, T. (2001). Increased glucocorticoid production and altered cortisol metabolism in women with mild to moderate Alzheimer’s disease. Biological Psychiatry, 49, 547–552.PubMedCrossRefGoogle Scholar
  116. Raymond, C. R. (2007). LTP forms 1, 2 and 3: Different mechanisms for the “long” in long-term potentiation. Trends in Neurosciences, 30, 167–175.PubMedCrossRefGoogle Scholar
  117. Reddy, P. H., & Beal, M. F. (2008). Amyloid beta, mitochondrial dysfunction and synaptic damage: Implications for cognitive decline in aging and Alzheimer’s disease. Trends in Molecular Medicine, 14, 45–53.PubMedCrossRefGoogle Scholar
  118. Reul, J. M., & de Kloet, E. R. (1985). Two receptor systems for corticosterone in rat brain: Microdistribution and differential occupation. Endocrinology, 117, 2505–2511.PubMedCrossRefGoogle Scholar
  119. Rodríguez, J. J., Jones, V. C., Tabuchi, M., Allan, S. M., Knight, E. M., LaFerla, F. M., et al. (2008). Impaired adult neurogenesis in the dentate gyrus of a triple transgenic mouse model of Alzheimer’s disease. PLoS One, 3(8):e2935.Google Scholar
  120. Romeo, R. D., Ali, F. S., Karatsoreos, I. N., Bellani, R., Chhua, N., Vernov, M., et al. (2008). Glucocorticoid receptor mRNA expression in the hippocampal formation of male rats before and after pubertal development in response to acute or repeated stress. Neuroendocrinology, 87, 160–167.PubMedCrossRefGoogle Scholar
  121. Roozendaal, B., Phillips, R. G., Power, A. E., Brooke, S. M., Sapolsky, R. M., & McGaugh, J. L. (2001). Memory retrival impairment induced by hippocampal CA3 lesions is blocked by adrenocortical suppression. Nature Neuroscience, 4, 1169–1171.PubMedCrossRefGoogle Scholar
  122. Sapolsky, R. M. (1986). Glucocorticoid toxicity in the hippocampus: Reversal by supplementation with brain fuels. Journal of Neuroscience, 6, 2240–2244.PubMedGoogle Scholar
  123. Sapolsky, R. M., Krey, L. C., & McEwen, B. S. (1986). The neuroendocrinology of stress and aging: The glucocorticoid cascade hypothesis. Endocrine Reviews, 7, 284–301.PubMedCrossRefGoogle Scholar
  124. Saxe, M. D., Battaglia, F., Wang, J. W., Malleret, G., David, D. J., Monckton, J. E., et al. (2006). Ablation of hippocampal neurogenesis impairs contextual fear conditioning and synaptic plasticity in the dentate gyrus. Proceedings of the National Academy of Sciences of the United States of America, 103, 17501–17506.PubMedCrossRefGoogle Scholar
  125. Sayer, R., Robertson, D., Balfour, D. J., Breen, K. C., & Stewart, C. A. (2008). The effect of stress on the expression of the amyloid precursor protein in rat brain. Neuroscience Letters, 431, 197–200.PubMedCrossRefGoogle Scholar
  126. Scheff, S. W., Price, D. A., Schmitt, F. A., DeKosky, S. T., & Mufson, E. J. (2007). Synaptic alterations in CA1 in mild Alzheimer disease and mild cognitive impairment. Neurology, 68, 1501–1508.PubMedCrossRefGoogle Scholar
  127. Scheff, S. W., Price, D. A., Schmitt, F. A., & Mufson, E. J. (2006). Hippocampal synaptic loss in early Alzheimer’s disease and mild cognitive impairment. Neurobiology of Aging, 27, 1372–1384.PubMedCrossRefGoogle Scholar
  128. Selkoe, D. J. (2002). Alzheimer’s disease is a synaptic failure. Science, 298, 789–791.PubMedCrossRefGoogle Scholar
  129. Selkoe, D. J. (2008). Soluble oligomers of the amyloid beta-protein impair synaptic plasticity and behavior. Behavioural Brain Research, 192, 106–113.PubMedCrossRefGoogle Scholar
  130. Shankar, G. M., Li, S., Mehta, T. H., Garcia-Munoz, A., Shepardson, N. E., Smith, I., et al. (2008). Amyloid-beta protein dimers isolated directly from Alzheimer’s brains impair synaptic plasticity and memory. Nature Medicine, 14, 837–842.PubMedCrossRefGoogle Scholar
  131. Shao, C., Xiong, S., Li, G. M., Gu, L., Mao, G., Markesbery, W. R., et al. (2008). Altered 8-oxoguanine glycosylase in mild cognitive impairment and late-stage Alzheimer’s disease brain. Free Radical Biology and Medicine, 45, 813–819.PubMedCrossRefGoogle Scholar
  132. Sheline, Y. I., Gado, M. H., & Kraemer, H. C. (2003). Untreated depression and hippocampal volume loss. American Journal of Psychiatry, 160, 1516–1518.PubMedCrossRefGoogle Scholar
  133. Sheline, Y. I., Wang, P. W., Gado, M. H., Csernansky, J. G., & Vannier, M. W. (1996). Hippocampal atrophy in recurrent major depression. Proceedings of the National Academy of Sciences of the United States of America, 93, 3908–3913.PubMedCrossRefGoogle Scholar
  134. Sheng, M., & Kim, M. J. (2002). Postsynaptic signaling and plasticity mechanisms. Science, 298, 776–780.PubMedCrossRefGoogle Scholar
  135. Shors, T. J., Seib, T. B., Levine, S., & Thompson, R. F. (1989). Inescapable versus escapable foot shock modulates long-term potentiation in the rat hippocampus. Science, 244, 224–226.PubMedCrossRefGoogle Scholar
  136. Simon, M., Czéh, B., & Fuchs, E. (2005). Age-dependent susceptibility of adult hippocampal cell proliferation to chronic psychosocial stress. Brain Research, 1049, 244–248.PubMedCrossRefGoogle Scholar
  137. Singh, A., & Kumar, A. (2008). Protective effect of alprazolam against sleep deprivation-induced behavior alterations and oxidative damage in mice. Neuroscience Research, 60, 372–379.PubMedCrossRefGoogle Scholar
  138. Smith, C., & Kelly, G. (1988). Paradoxical sleep deprivation applied two days after end of training retards learning. Physiology & Behavior, 43, 213–216.CrossRefGoogle Scholar
  139. Smith, M. A., Makino, S., Kvetnansky, R., & Post, R. M. (1995). Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus. Journal of Neuroscience, 15, 1768–1777.PubMedGoogle Scholar
  140. Smith-Swintosky, V. L., Pettigrew, L. C., Sapolsky, R. M., Phares, C., Craddock, S. D., Brooke, S. M., et al. (1996). Metyrapone, an inhibitor of glucocorticoid production, reduces brain injury induced by focal and global ischemia and seizures. Journal of Cerebral Blood Flow and Metabolism, 16, 585–598.PubMedGoogle Scholar
  141. Snyder, J. S., Hong, N. S., McDonald, R. J., & Wojtowicz, J. M. (2005). A role for adult neurogenesis in spatial long-term memory. Neuroscience, 130, 843–852.PubMedCrossRefGoogle Scholar
  142. Sotiropoulos, I., Cerqueira, J. J., Catania, C., Takashima, A., Sousa, N., & Almeida, O. F. X. (2008). Stress and glucocorticoid footprints in the brain- the path from depression to Alzheimer’s disease. Neuroscience and Biobehavioral Reviews, 32, 1161–1173.PubMedCrossRefGoogle Scholar
  143. Sousa, N., Lukoyanov, N. V., Madeira, M. D., Almeida, O. F., & Paula-Barbosa, M. M. (2000). Reorganization of the morphology of hippocampal neurites and synapses after stress-induced damage correlates with behavioral improvement. Neuroscience, 97, 253–266.PubMedCrossRefGoogle Scholar
  144. Srivareerat, M., Tran, T. T., Alzoubi, K. H., & Alkadhi, K. A. (2009). Chronic psychosocial stress exacerbates impairment of cognition and long-term potentiation in β-amyloid rat model of Alzheimer’s disease. Biological Psychiatry, 65, 918–926.PubMedCrossRefGoogle Scholar
  145. Sterlemann, V., Rammes, G., Wolf, M., Liebl, C., Ganea, K., Müller, M. B., et al. (2009) Chronic social stress during adolescence induces cognitive impairment in aged mice. Hippocampus (in press).Google Scholar
  146. Stranahan, A. M., Arumugam, T. V., Cutler, R. G., Lee, K., Egan, J. M., & Mattson, M. P. (2008a). Diabetes impairs hippocampal function through glucocorticoid-mediated effects on new and mature neurons. Nature Neuroscience, 11, 309–317.PubMedCrossRefGoogle Scholar
  147. Stranahan, A. M., Lee, K., Becker, K. G., Zhang, Y., Maudsley, S., Martin, B., et al. (2008b). Hippocampal gene expression patterns underlying the enhancement of memory by running in aged mice. Neurobiol Aging (in press).Google Scholar
  148. Stranahan, A. M., Lee, K., Martin, B., Maudsley, S., Golden, E., Cutler, R. G., et al. (2009). Voluntary exercise and caloric restriction enhance hippocampal dendritic spine density and BDNF levels in diabetic mice. Hippocampus (in press).Google Scholar
  149. Stranahan, A. M., & Mattson, M. P. (2008). Impact of energy intake and expenditure on neuronal plasticity. Neuromolecular Medicine, 10, 209–218.PubMedCrossRefGoogle Scholar
  150. Sullivan, P. G., Geiger, J. D., Mattson, M. P., & Scheff, S. W. (2000). Dietary supplement creatine protects against traumatic brain injury. Annals of Neurology, 48, 723–729.PubMedCrossRefGoogle Scholar
  151. Tadavarty, R., Kaan, T. K., & Sastry, B. R. (2009). Long-term depression of excitatory synaptic transmission in rat hippocampal CA1 neurons following sleep-deprivation. Experimental Neurology, 216, 239–242.PubMedCrossRefGoogle Scholar
  152. Tiba, P. A., Oliveira, M. G., Rossi, V. C., Tufik, S., & Suchecki, D. (2008). Glucocorticoids are not responsible for paradoxical sleep deprivation-induced memory impairments. Sleep, 31, 505–515.PubMedGoogle Scholar
  153. Touma, C., Ambrée, O., Görtz, N., Keyvani, K., Lewejohann, L., Palme, R., et al. (2004). Age- and sex-dependent development of adrenocortical hyperactivity in a transgenic mouse model of Alzheimer’s disease. Neurobiology of Aging, 25, 893–904.PubMedCrossRefGoogle Scholar
  154. Trimmer, P. A., Keeney, P. M., Borland, M. K., Simon, F. A., Almeida, J., Swerdlow, R. H., et al. (2004). Mitochondrial abnormalities in cybrid cell models of sporadic Alzheimer’s disease worsen with passage in culture. Neurobiology of Diseases, 15, 29–39.CrossRefGoogle Scholar
  155. Umegaki, H., Ikari, H., Nakahata, H., Endo, H., Suzuki, Y., Ogawa, O., et al. (2000). Plasma cortisol levels in elderly female subjects with Alzheimer’s disease: A cross-sectional and longitudinal study. Brain Research, 881, 241–243.PubMedCrossRefGoogle Scholar
  156. Valla, J., Schneider, L., Niedzielko, T., Coon, K. D., Caselli, R., Sabbagh, M. N., et al. (2006). Impaired platelet mitochondrial activity in Alzheimer’s disease and mild cognitive impairment. Mitochondrion, 6, 323–330.PubMedCrossRefGoogle Scholar
  157. van Praag, H. (2009). Exercise and the brain: Something to chew on. Trends in Neurosciences, 32, 283–290.PubMedCrossRefGoogle Scholar
  158. van Praag, H., Schinder, A. F., Christie, B. R., Toni, N., Palmer, T. D., & Gage, F. H. (2002). Functional neurogenesis in the adult hippocampus. Nature, 415, 1030–1034.PubMedCrossRefGoogle Scholar
  159. van Praag, H., Shubert, T., Zhao, C., & Gage, F. H. (2005). Exercise enhances learning and hippocampal neurogenesis in aged mice. Journal of Neuroscience, 25, 8680–8685.PubMedCrossRefGoogle Scholar
  160. Walsh, D. M., Klyubin, I., Fadeeva, J. V., Cullen, W. K., Anwyl, R., Wolfe, M. S., et al. (2002). Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature, 416, 535–539.PubMedCrossRefGoogle Scholar
  161. Watanabe, Y., Gould, E., Cameron, H. A., Daniels, D. C., & McEwen, B. S. (1992). Phenytoin prevents stress- and corticosterone-induced atrophy of CA3 pyramidal neurons. Hippocampus, 2, 431–436.PubMedCrossRefGoogle Scholar
  162. Watson, D., & Clark, L. A. (1984). Negative affectivity: The disposition to experience aversive emotional states. Psychological Bulletin, 96, 465–490.PubMedCrossRefGoogle Scholar
  163. Weiss, A., Sutin, A. R., Duberstein, P. R., Friedman, B., Bagby, R. M., & Costa, P. T., Jr. (2009). The personality domains and styles of the five-factor model are related to incident depression in Medicare recipients aged 65 to 100. The American Journal of Geriatric Psychiatry, 17, 591–601.PubMedCrossRefGoogle Scholar
  164. West, M. J., Coleman, P. D., Flood, D. G., & Troncoso, J. C. (1994). Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer’s disease. Lancet, 344, 769–772.PubMedCrossRefGoogle Scholar
  165. West, M. J., Kawas, C. H., Martin, L. J., & Troncoso, J. C. (2000). The CA1 region of the human hippocampus is a hot spot in Alzheimer’s disease. Annals of the New York Academy of Sciences, 908, 255–259.PubMedCrossRefGoogle Scholar
  166. Wilson, R. S., Arnold, S. E., Schneider, J. A., Kelly, J. F., Tang, Y., & Bennett, D. A. (2006). Chronic psychological distress and risk of Alzheimer’s disease in old age. Neuroepidemiology, 27, 143–153.PubMedCrossRefGoogle Scholar
  167. Wilson, R. S., Arnold, S. E., Schneider, J. A., Li, Y., & Bennett, D. A. (2007). Chronic distress, age-related neuropathology, and late-life dementia. Psychosomatic Medicine, 69, 47–53.PubMedCrossRefGoogle Scholar
  168. Wisor, J. P., Edgar, D. M., Yesavage, J., Ryan, H. S., McCormick, C. M., Lapustea, N., et al. (2005). Sleep and circadian abnormalities in a transgenic mouse model of Alzheimer’s disease: A role for cholinergic transmission. Neuroscience, 131, 375–385.PubMedCrossRefGoogle Scholar
  169. Wolf, O. T. (2009). Stress and memory in humans: Twelve years of progress? Brain Research (in press).Google Scholar
  170. Woolley, C. S., Gould, E., & McEwen, B. S. (1990). Exposure to excess glucocorticoids alters dendritic morphology of adult hippocampal pyramidal neurons. Brain Research, 531, 225–231.PubMedCrossRefGoogle Scholar
  171. Yao, Y. Y., Liu, D. M., Xu, D. F., & Li, W. P. (2007). Memory and learning impairment induced by dexamethasone in senescent but not young mice. European Journal of Pharmacology, 574, 20–28.PubMedCrossRefGoogle Scholar
  172. Yap, J. J., Takase, L. F., Kochman, L. J., Fornal, C. A., Miczek, K. A., & Jacobs, B. L. (2006). Repeated brief social defeat episodes in mice: Effects on cell proliferation in the dentate gyrus. Behavioural Brain Research, 172, 344–350.PubMedCrossRefGoogle Scholar
  173. Yatin, S. M., Aksenov, M., & Butterfield, D. A. (1999). The antioxidant vitamin E modulates amyloid beta-peptide-induced creatine kinase activity inhibition and increased protein oxidation: Implications for the free radical hypothesis of Alzheimer’s disease. Neurochemical Research, 24, 427–435.PubMedCrossRefGoogle Scholar
  174. Youngblood, B. D., Zhou, J., Smagin, G. N., Ryan, D. H., & Harris, R. B. (1997). Sleep deprivation by the “flower pot” technique and spatial reference memory. Physiology & Behavior, 61, 249–256.CrossRefGoogle Scholar
  175. Zafir, A., & Banu, N. (2009). Modulation of in vivo oxidative status by exogenous corticosterone and restraint stress in rats. Stress, 12, 167–177.PubMedCrossRefGoogle Scholar
  176. Zhang, C., McNeil, E., Dressler, L., & Siman, R. (2007). Long-lasting impairment in hippocampal neurogenesis associated with amyloid deposition in a knock-in mouse model of familial Alzheimer’s disease. Experimental Neurology, 204, 77–87.PubMedCrossRefGoogle Scholar
  177. Zhou, J., Zhang, F., & Zhang, Y. (2000). Corticosterone inhibits generation of long-term potentiation in rat hippocampal slice: Involvement of brain-derived neurotrophic factor. Brain Research, 885, 182–191.PubMedCrossRefGoogle Scholar

Copyright information

© US Government 2009

Authors and Affiliations

  1. 1.Laboratory of Neurosciences, National Institute on Aging Intramural Research ProgramBaltimoreUSA

Personalised recommendations