Table 1.
Summary of current research on the effects of chronic stress in various models of AD.
| Outcome | ||||
|---|---|---|---|---|
| AD model | Environmental Stress | Behavioral | Biochemical & Physiological | Reference |
| infusion of Aβ (rat) | • intruder psychosocial stress model (6 weeks) | • chronic stress worsens Aβ-induced deficits in spatial learning | • stress exacerbates impairment of early phase LTP in Aβ treated rats | Srivareerat et al., Biol Psychiat 2009 |
| • stress reduces basal levels of phosphorylated calcium/calmodulin dependent protein kinase II and increases basal calcineurin after Aβ infusion | ||||
| infusion of Aβ (rat) | • chronic unpredictable stress (4 weeks) • dex administration |
• chronic stress and dex both exacerbate Aβ-induced deficits in spatial learning | • stress and dex magnify increases in C99, BACE-1 and nicastrin induced by Aβ in the hippocampus and cortex | Catania et al., Mol Psychiat 2009 |
| • chronic stress and dex administration | • Aβ, stress and dex all induce anxiety but the effect is not compounded by their combination | |||
| APPV717I-CT100 (mouse) | • immobilization stress (6 or 8 months) | • stress accelerates learning and memory impairments in a passive avoidance paradigm and social transfer of food preference test | • stress increases extracellular amyloid plaques and intraneuronal Aβ deposition in the hippocampus | Jeong et al., FASEB 2006 |
| Tg 2576 (mouse) | • stress increases tau phosphorylation in the hippocampus and cortex | |||
| Tg 2576 (mouse) | • social isolation (6 months) | • social isolation accelerates the onset of memory impairments in contextual, but not cued, fear conditioning | • social isolation accelerates deposition of Aβ plaques in the hippocampus | Dong et al., Neuroscience 2004 |
| • social isolation exacerbates the decrease in hippocampal neurogenesis in AD | ||||
| Tg 2576 (mouse) | • social isolation (6 months) | • social isolation increases basal cort | Dong et al., Neuroscience 2008 | |
| • social isolation increases expression of GR in the cortex and CRF1 in the cortex and hippocampus | ||||
| • social isolation increases Aβ plaque deposition | ||||
| Tg 2576 (mouse) | • restraint stress (16 days) | • restraint increases plasma cort | Lee et al., J Neurochem 2009 | |
| • chronic restraint increases Aβ plaque deposition in the cortex, tau hyperphosphorylation and metabolic oxidative stress | ||||
| • chronic restraint downregulates expression of MMP-2 | ||||
| 3xTgAD (mouse) | • dex administration (7 days) | • basal plasma corticosterone is elevated in 3xTgAD mice | Green et al., J Neurosci 2006 | |
| • dex increases intraneuronal Aβ, total APP, C99 and BACE | ||||
| • dex accelerates accumulation of tau in dendrites | ||||
Abbreviations: AD (Alzheimer's Disease); dex (dexamethasone); LTP (long term potentiation); C99 (C-terminal fragment 99); BACE-1 (β-site APP-cleaving enzyme) cort (corticosterone); CRF1 (corticotropin releasing factor); MMP2 (matrix metalloproteinase 2); APP (amyloid precursor protein); GR (glucocorticoid receptor)