Intermittent Calorie Restriction Ameliorates Behavioral Changes and Tau Hyperphosphorylation in Chronic Immobilization Stress in Rats.

Abstract

Background: Chronic stress has been linked to mood and anxiety disorders and alteration of cognitive functions, such as memory. Intermittent calorie restriction (ICR) is a repeated mild stress that enhances the cell ability to combat more severe stress. Aim: Examination of the effects of ICR on rat behaviour and Tau hyperphosphorylation in chronic immobilization stress (CIS) rat model. Methods: 32 rats were divided into 4 equal groups: control, ICR (subjected to ICR protocol), CIS (subjected to CIS protocol), and CIS+ICR (subjected to both CIS and ICR protocols). After performing behavioural (open field and Barnes maze) tests, serum level of corticosterone, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined, and hippocampal tissue level of phosphorylated Tau (phospho-Tau), noradrenaline, and serotonin were measured. Results: We found that, ICR significantly altered the stress-induced anxiety-like behavior and memory disturbances (P<0.001). Rats exposed to both ICR and CIS protocols had significantly lower levels of phospho-Tau, corticosterone, and TNF-α, and enhanced levels of noradrenaline and serotonin than those subjected to CIS alone (P<0.01). Conclusion: our results suggest that ICR protects against chronic stress-induced anxiety-like behaviour, memory disturbance and Tau hyperphosphorylation, possibly through inhibition of hypothalamic pituitary adrenal (HPA) axis, anti-inflammatory effects, and enhancement of noradrenaline and serotonin hormones.