Microglia activation regulates GluR1 phosphorylation in chronic unpredictable stress-induced cognitive dysfunction

Abstract

Chronic stress is considered to be a major risk factor in the development of psychopathological syndromes in humans. Cognitive impairments and long-term potentiation (LTP) impairments are increasingly recognized as major components of depression, anxiety disorders and other stress-related chronic psychological illnesses. It seems timely to systematically study the potentially underlying neurobiological mechanisms of altered cognitive and synaptic plasticity in the course of chronic stress. In the present study, a rat model of chronic unpredictable stress (CUS) induced a cognitive impairment in spatial memory in the Morris water maze (MWM) test and a hippocampal LTP impairment. CUS also induced hippocampal microglial activation and attenuated phosphorylation of glutamate receptor 1 (GluR1 or GluA1). Moreover, chronic treatment with the selective microglial activation blocker, minocycline (120 mg/kg per day), beginning 3 d before CUS treatment and continuing through the behavioral testing period, prevented the CUS-induced impairments of spatial memory and LTP induction. Additional studies showed that minocycline-induced inhibition of microglia activation was associated with increased phosphorylation of GluR1. These results suggest that hippocampal microglial activation modulates the level of GluR1 phosphorylation and might play a causal role in CUS-induced cognitive and LTP disturbances.

• Cognition
• glutamate receptor
• hippocampus
• long-term potentiation
• microglia
• stress

Declaration of interest

This work was supported by grants from the National Key Technology R&D Program (2009BAI85B04); National Basic Research Program of China (973 Program, #2012CB525002); National Natural Science Foundation of China (#81172621, #30901173); Program for New Century Excellent Talents in University; Science and Technology Innovation Projects of Shaanxi Province (#2011KTCL03-19). This work was also supported by Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT); Program of Public Welfare, Ministry of Health, China (No. 200902006). The authors have no financial or other interests with regard to the article that represent a conflict of interest. None of the funding organizations listed above had any role in the design or conduct of the study, the data analysis, in the preparation of the manuscript or in the decision to submit the work for publication.

Supplementary data available online

Figure S1. The distance covered before and after escape latency trail.

Figure S2. Morris water maze schematic diagram.

Figure S3. Lead exposure induced microglia activation.