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 Alzheimer's 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.

• Authors: C Yang, X Guo, G H Wang, H L Wang, Z C Liu, H Liu, Z X Zhu, Y Li
• Journal: Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas (Braz J Med Biol Res) Vol. 47 Issue 3 Pg. 237-44 (Feb 2014) ISSN: 1414-431X [Electronic] Brazil
• PMID: 24652321 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antidepressive Agents, Second-Generation
• tau Proteins
• Fluoxetine

Topics

• Alzheimer Disease (complications)
• Analysis of Variance
• Anhedonia
• Animals
• Antidepressive Agents, Second-Generation (therapeutic use)
• Depression (complications, drug therapy, metabolism)
• Fluoxetine (therapeutic use)
• Food Preferences (psychology)
• Frontal Lobe (metabolism)
• Hippocampus (metabolism)
• Male
• Phosphorylation
• Rats, Sprague-Dawley
• Stress, Psychological (complications, drug therapy, metabolism)
• tau Proteins (metabolism)