EFFECTS OF ACUTE RESTRAINT STRESS ON SYNAPTIC AND COGNITIVE FUNCTION

Abstract

Acute restraint stress (ARS) has been known to affect hippocampal related functions but the extent to which its impact on molecular and structural functions are yet to be investigated. We thus established a single 6-h restraint stress protocol to delve into the intricate mechanism of the early cellular signaling changes and structural remodeling mechanism in the hippocampus of C57BL/6J mice. Cognitive behavioral assessments illustrated the improved spatial memory-related function represented by increased spontaneous alternation in Y-maze and intact recognition memory shown by novel object recognition (NOR) testing. By implementing immunoblotting and ultrastructural imaging techniques, we observed a transient acute alternation of the eukaryotic elongation factor 2 (eEF2) and eukaryotic initiation factor 4E binding protein 1 (4E-BP1) as well reduction of the mitochondria densities. In addition, we noticed significant changes of morphological remodeling of the dendritic spines characterized by increased proportions of mushroom-like spines and reduction of filopedia-like structures by Golgi-Cox staining. These findings suggest that 6-h ARS exposure was adequate to alter short-term molecular signaling in the dendritic structures in hippocampus and may imply its functional role in the improvement of the working memory we observed.

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Acute Restraint Stress, Dendritic Spines, Memory, Protein Synthesis, Synaptic Plasticity

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Wake Forest University