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Review
, 12 (1), 56-70

Adverse Stress, Hippocampal Networks, and Alzheimer's Disease

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Review

Adverse Stress, Hippocampal Networks, and Alzheimer's Disease

Sarah M Rothman et al. Neuromolecular Med.

Abstract

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.

Figures

Figure 1
Figure 1
Schematic showing the components of the HPA axis (A). Activation of the HPA axis results in release of glucocorticoids (corticosterone in rodents, cortisol in humans). The CA3 region of the hippocampus inhibits activation of the HPA axis. Schematic of the hippocampus showing areas CA1, CA3 and the dentate gyrus (B). Specific sites of hippocampal plasticity as well as control of the HPA axis and the site of glucocorticoid receptors (GR) are noted.
Figure 1
Figure 1
Schematic showing the components of the HPA axis (A). Activation of the HPA axis results in release of glucocorticoids (corticosterone in rodents, cortisol in humans). The CA3 region of the hippocampus inhibits activation of the HPA axis. Schematic of the hippocampus showing areas CA1, CA3 and the dentate gyrus (B). Specific sites of hippocampal plasticity as well as control of the HPA axis and the site of glucocorticoid receptors (GR) are noted.
Figure 2
Figure 2
Pathways through which AD and chronic adverse stress potentially lead to cognitive impairments. Chronic stress and AD share similar pathways via increased release of glucocorticoids. Dashed arrows indicate that impairments in LTP, alterations in dendritic morphology and decreases in neurogenesis are all thought to lead to cognitive impairments although the exact mechanisms are not entirely known.

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