Article

The amyloidogenic potential and behavioral correlates of stress

Max Planck Institute of Psychiatry, Munich, Germany.
Molecular Psychiatry (Impact Factor: 14.5). 11/2007; 14(1):95-105. DOI: 10.1038/sj.mp.4002101
Source: PubMed

ABSTRACT

Observations of elevated basal cortisol levels in Alzheimer's disease (AD) patients prompted the hypothesis that stress and glucocorticoids (GC) may contribute to the development and/or maintenance of AD. Consistent with that hypothesis, we show that stress and GC provoke misprocessing of amyloid precursor peptide in the rat hippocampus and prefrontal cortex, resulting in increased levels of the peptide C-terminal fragment 99 (C99), whose further proteolytic cleavage results in the generation of amyloid-beta (Abeta). We also show that exogenous Abeta can reproduce the effects of stress and GC on C99 production and that a history of stress strikingly potentiates the C99-inducing effects of Abeta and GC. Previous work has indicated a role for Abeta in disruption of synaptic function and cognitive behaviors, and AD patients reportedly show signs of heightened anxiety. Here, behavioral analysis revealed that like stress and GC, Abeta administration causes spatial memory deficits that are exacerbated by stress and GC; additionally, Abeta, stress and GC induced a state of hyperanxiety. Given that the intrinsic properties of C99 and Abeta include neuroendangerment and behavioral impairment, our findings suggest a causal role for stress and GC in the etiopathogenesis of AD, and demonstrate that stressful life events and GC therapy can have a cumulative impact on the course of AD development and progression.

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Available from: Osborne F.X. Almeida, Dec 16, 2014
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    • "Thus, oxidative stress-mediated hippocampal neuronal degeneration underscores memory impairment due to chronic stress. However, there are suggestions that compounds with neuroprotective property may be of benefits in chronic stress-induced cognitive deficits and other neuropsychiatric disorders (Panossian, 2013; Rothman and Mattson 2010;Catania et al., 2009;Balkan et al., 2001;Patil et al., 2006). Therefore, it may be concluded that neuroprotection offered by MJ may also contribute significantly to its adaptogenic-like property in reversing memory deficits induced by UCMS in mice. "
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    ABSTRACT: This study was undertaken to evaluate the adaptogenic-like activity of methyl jasmonate (MJ) in mice exposed to unpredictable chronic mild stress (UCMS). Male Swiss mice were treated with MJ (25-100mg/kg, i.p.) 30min before exposure to UCMS daily for 14 days prior to testing for memory and anxiety. Thereafter, the blood glucose and serum corticosterone levels were estimated using glucometer and ELISA. The brain concentrations of malondialdehyde (MDA) and glutathione (GSH) were estimated using spectrophotometer. Brain histology and the population of healthy neurons in the hippocampal regions were also assessed. MJ reversed anxiety and memory impairment produced by UCMS, which suggest adaptogenic-like property. The reduction in the weight of adrenal gland and liver in MJ-treated groups further indicates adaptogenic activity. It further decreases the blood glucose and serum corticosterone levels in UCMS-mice. Also, MJ decreases the concentrations of MDA and elevated the levels of GSH in the brain of mice exposed to UCMS. Brain histology revealed that MJ attenuated UCMS-induced degeneration and death of neuronal cells in the pyramidal layer of the cornu ammonis 3 (CA3) and the sub-granular zone of the dentate gyrus of the hippocampus. Moreover, MJ decreased the population of dead neuronal cells of the pyramidal layer of the CA3 and the sub-granular zone of the dentate gyrus of the UCMS-mice, which suggests neuroprotection. Taken together, these findings suggest that MJ demonstrated adaptogenic-like activity in mice; which might be related to modulation of serum corticosterone levels, inhibition of oxidative stress and neuroprotection.
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    • "In various preclinical AD models, stress worsens deficits in hippocampus-dependent spatial learning (Catania et al, 2009; Cuadrado-Tejedor et al, 2012; Dong et al, 2004; Jeong et al, 2006; Srivareerat et al, 2009; Tran et al, 2010). These deleterious effects are in part caused by an accelerated accumulation of Ab under stressing conditions (Catania et al, 2009; Cuadrado-Tejedor et al, 2012; Dong et al, 2004; Green et al, 2006; Jeong et al, 2006; Srivareerat "
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    No preview · Article · Jan 2015 · Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology
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    • "Aside from SI, other manners of chronic stresses, such as chronic immobilization stress (Jeong et al., 2006) and mild unpredictable chronic stress (Cuadrado-Tejedor et al., 2012), exacerbate amyloid production in transgenic mouse models of AD. Furthermore, unpredictable chronic stress can also alter APP metabolism toward the amyloidogenic pathway in normal, middle-aged rats (Catania et al., 2009). These studies highlight that various stresses, including SI, stimulate increases in the amyloidogenic pathway. "
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