Changes in Hippocampal Androgen Receptor Density and Behavior in Sprague-Dawley Male Rats Exposed to a Low-Pressure Blast Wave

Jay R Hoffman; Amitai Zuckerman; Omri Ram; Oren Sadot; Hagit Cohen

doi:10.3233/BPL-200107

Changes in Hippocampal Androgen Receptor Density and Behavior in Sprague-Dawley Male Rats Exposed to a Low-Pressure Blast Wave

Brain Plast. 2020 Oct 1;5(2):135-145. doi: 10.3233/BPL-200107.

Authors

Jay R Hoffman¹, Amitai Zuckerman², Omri Ram³, Oren Sadot⁴, Hagit Cohen²

Affiliations

¹ Department of Physical Therapy, Ariel University, Ariel, Israel.
² Anxiety and Stress Research Unit, Beer-Sheva Mental Health Center, Faculty of Health Sciences, Division of Psychiatry, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
³ Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD, USA.
⁴ Department of Mechanical Engineering, Ben-Gurion University, Israel.

Abstract

Objective: The purpose of this study was to examine the effect of exposure of a low-intensity blast wave on androgen receptor (AR) density in the hippocampus and the potential influence on behavioral and cognitive responses.

Methods: Sprague-Dawley rats were randomly assigned to either a blast exposed group (n = 27) or an unexposed (control) group (n = 10). Animals were treated identically, except that rats within the control group were not exposed to any of the characteristics of the blast wave. Behavior measures were conducted on day seven post-exposure. The rats were initially assessed in the elevated plus maze followed by the acoustic startle response paradigm. Spatial memory performance using the Morris water-maze test was assessed at 8-days post-exposure, for seven consecutive days. Following all behavioral tests AR immunofluorescence staining was performed in different hippocampal subregions.

Results: A significant elevation in anxiety index (p < 0.001) and impaired learning (p < 0.015) and spatial memory (p < 0.0015) were noted in exposed rats. In addition, a significant attenuation of the AR was noted in the CA1 (p = 0.006) and dentate gyrus (p = 0.031) subregions of the hippocampus in blast exposed animals. Correlational analyses revealed significant associations between AR and both anxiety index (r = -.36, p = 0.031) and memory (r = -0.38, p = 0.019).

Conclusions: The results of this study demonstrate that exposure to a low-pressure blast wave resulted in a decrease in AR density, which was associated with significant behavioral and cognitive changes.

Keywords: Testosterone; mTBI; military; neurotrauma; stress.