Chronic psychosocial stress exposes Alzheimer s disease phenotype in a novel at-risk model

10.2741/e371 ◽  
2012 ◽  
Vol E4 (1) ◽  
pp. 214-229 ◽  
Author(s):  
Karim A Alkadhi
US Neurology ◽  
2010 ◽  
Vol 06 (01) ◽  
pp. 32 ◽  
Author(s):  
Karim A Alkadhi ◽  

Apart from genetic factors, environmental factors such as stress may also play a critical role in the manifestation of Alzheimer’s disease (AD). We studied the impact of chronic psychosocial stress in two amyloid-beta (Aβ) rat models of AD by three approaches: learning and memory tests in the radial arm water maze, electrophysiological recordings of long-term potentiation (LTP) in anesthetized rats, and immunoblot analysis of synaptic plasticity- and cognition-related signaling molecules. The first Aβ rat model, representing established AD, was induced by continuous intracerebroventricular (ICV) infusion of a pathogenic dose of Aβ peptides via a 14-day osmotic pump. In this AD model, chronic stress intensified cognitive deficits, produced more depression of LTP, and accentuated the reduction of signaling molecule levels compared with the established model alone. The second model represents subjects that are clinically normal but are at risk for AD, and was induced by ICV infusion of a sub-threshold (sub-Aβ) dose of Aβ peptides. Chronic psychosocial stress was induced using a rat intruder model. Various tests showed that sub-Aβ rats were not significantly different from control rats. However, chronically stressed sub-Aβ rats showed more significant impairment of cognitive functions and early-phase LTP than that caused by stress alone. Molecular analysis revealed marked disturbances in the levels of essential signaling molecules in the stressed AD at-risk rats. These findings suggest that chronic stress may profoundly accelerate and intensify the impairment of cognition and synaptic plasticity in individuals at risk for AD and those with established AD, respectively. Possible mechanisms for the effect of chronic stress are discussed.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Guy A. Prochilo ◽  
Ricardo J.S. Costa ◽  
Craig Hassed ◽  
Richard Chambers ◽  
Pascal Molenberghs

Abstract Objectives Researchers have begun delivering mindfulness and aerobic exercise training concurrently on the premise that a combination intervention will yield salutary outcomes over and above each intervention alone. An estimate of the effect of combination training on chronic psychosocial stress in a nonclinical population has not been established. The objective of this study was to establish protocol feasibility in preparation of a definitive RCT targeting healthy individuals, and to explore the preliminary effect of combination training on reducing chronic psychosocial stress in this population. Methods Twenty-four participants were allocated to a single-arm pre-post study and subjected to 16 weeks of concurrent mindfulness psychoeducation and aerobic exercise training. Feasibility criteria were collected and evaluated. Within-group changes in chronic psychosocial stress, mindfulness, emotion regulation, and cardiorespiratory fitness were also assessed. Primary analyses were based on 17 participants. Results Retention rate, response rate, recruitment rate, and sample size analyses indicate a definitive trial is feasible for detecting most effects with precision. There was also a decline in our primary dependent measure of chronic psychosocial stress (dpretest = −0.56, 95% CI [ −1.14,−0.06]). With regard to secondary measures, there was an increase in the use of cognitive reappraisal, and a reduction in use of maladaptive emotion regulation strategies. We are insufficiently confident to comment on changes in mindfulness and aerobic capacity $\left (\dot {V}O_{2max}\right)$ V ̇ O 2 max . However, there were subgroup improvements in aerobic economy at submaximal exercise intensities. Conclusions We recommend a definitive trial is feasible and should proceed. Trial registration ANZCTR (ID: ACTRN12619001726145). Retrospectively registered December 9, 2019.


2016 ◽  
Vol 32 (5) ◽  
pp. 235-240
Author(s):  
Ana Starcevic ◽  
Sasa Petricevic ◽  
Zoran Radojicic ◽  
Vuk Djulejic ◽  
Andrej Ilankovic ◽  
...  

2016 ◽  
Vol 451 ◽  
pp. 113-122 ◽  
Author(s):  
Hojin Lee ◽  
Jae Wook Song ◽  
Woojin Chang
Keyword(s):  
At Risk ◽  

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