Changes in tau phosphorylation levels in the hippocampus and frontal cortex following chronic stress

Abstract

Studies have indicated that early-life or early-onset depression is associated with a 2- to 4-fold increased risk of developing Alzheimers disease (AD). In AD, aggregation of an abnormally phosphorylated form of the tau protein may be a key pathological event. Tau is known to play a major role in promoting microtubule assembly and stabilization, and in maintaining the normal morphology of neurons. Several studies have reported that stress may induce tau phosphorylation. The main aim of the present study was to investigate possible alterations in the tau protein in the hippocampus and frontal cortex of 32 male Sprague-Dawley rats exposed to chronic unpredictable mild stress (CUMS) and then re-exposed to CUMS to mimic depression and the recurrence of depression, respectively, in humans. We evaluated the effects of CUMS, fluoxetine, and CUMS re-exposure on tau and phospho-tau. Our results showed that a single exposure to CUMS caused a significant reduction in sucrose preference, indicating a state of anhedonia. The change in behavior was accompanied by specific alterations in phospho-tau protein levels, but fluoxetine treatment reversed the CUMS-induced impairments. Moreover, changes in sucrose preference and phospho-tau were more pronounced in rats re-exposed to CUMS than in those subjected to a single exposure. Our results suggest that changes in tau phosphorylation may contribute to the link between depression and AD.

Long-term Ameliorative Effects of the Antidepressant Fluoxetine Exposure on Cognitive Deficits in 3 × TgAD Mice

“…The underlying mechanisms may be associated with fluoxetine reducing the cleavage of APP, which awaits further study. Recent study reported that fluoxetine treatment also reduced the phospho-tau protein levels in Sprague Dawley rats exposed to chronic unpredictable mild stress [22]. However, our results displayed that fluoxetine treatment had no significant influence on the phosphotau protein levels.…”

“…In addition, some researches also noticed that fluoxetine could decrease the production of Aβ and protect against amyloid-beta toxicity [19][20][21]. A recent study manifested that fluoxetine also suppresses tau hyperphosphorylation in rats exposed to unpredictable chronic mild stress [22]. In all the above studies, behavioral tests and biochemical assays were detected immediately after drug withdrawal.…”

Antidepressant, anxiolytic and procognitive effects of rivastigmine and donepezil in the chronic mild stress model in rats

“…The impairment of object recognition performance by CMS, and its remediation by chronic antidepressant treatment, is consistent with earlier findings (Orsetti et al 2007 ; Elizalde et al 2008 ; Briones et al 2012 ; Solas et al 2013 ). In aged animals, CMS also increases biochemical markers associated with Alzheimer’s disease (El-faramawy et al 2009 ; Briones et al 2012 ; Solas et al 2013 ; Yang et al 2014 ), indicating that, in addition to its utility as an animal model of depression, the CMS procedure may have value as a model to investigate the early stages of dementia (e.g. Cuadrado-Tejedor et al 2012 ; Lisowski et al 2013 ).…”

Concurrent Mild Traumatic Brain Injury and Posttraumatic Stress Disorder Is Associated With Elevated Tau Concentrations in Peripheral Blood Plasma

“…Furthermore, preclinical models in both transgenic and nontransgenic rodent models have indicated that chronic stress leads to increased cortical accumulation of both Aβ and abnormal hyperphosphorylation of tau (Catania et al., ; Dong et al., ). Specifically, Yang and colleagues () showed that following chronic stress, phosphorylated tau was found in the hippocampus and frontal cortex, with associated alterations in behavior. Therefore, there is a possibility that tau and Aβ may contribute to the link between PTSD and dementia.…”