Insight Into Posttraumatic Stress Disorder: A Behavioral and Molecular Comparison Between Male and Female Mice Exposed to Stress-Enhanced Fear Learning
Open Access
- Author:
- Mc Kenna, Alexandria
- Area of Honors:
- Biology
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Janine Kwapis, Thesis Supervisor
Bernhard Luscher, Thesis Honors Advisor - Keywords:
- Posttraumatic stress disorder
Stress-enhanced fear learning
Sex difference
BDNF
Gria1
Hippocampus
Amygdala - Abstract:
- Posttraumatic stress disorder (PTSD), a trauma- and stress-related disorder, consists of emotional and behavioral changes in people following one or more traumatic experiences. According to epidemiological research, PTSD is disproportionately prevalent among the adult population. Specifically, more women are likely to develop PTSD than men – 8% of women compared to 4% of men at some point in their lives (U.S. Department of Veterans Affairs, 2023). Despite this sex difference persisting over several decades, minimal research provides insight into casual factors, with even less work focusing on molecular factors compared to situational factors. Consequently, this present study aimed to elucidate the roles of candidate genes behind the sex difference in fear learning through a reliable rodent model of PTSD known as the stress-enhanced fear learning (SEFL) procedure. Since the standard SEFL procedure elicits an effect strong enough to mask underlying sex differences, as indicted by some of our previous work, the SEFL procedure was first modified by decreasing the number and intensity of administered footshocks. Once we confirmed that the modified SEFL procedure engendered a sex difference in murine fear learning, another cohort of mice only underwent the first and second phases of the modified SEFL procedure to pinpoint any molecular effects of weak stress history on fear learning. From there, the mice were sacrificed for hippocampus and amygdala extractions due to the relevance of these brain regions in the SEFL research literature. With the brain tissues, RT-qPCR analyses were conducted to quantify the expressions of transcripts mapping to BDNF exons I, IV, and IX and of the Gria1 gene; like the brain regions, these genes were selected due to their relevance in the SEFL research literature. We found that hippocampal BDNF transcripts are correlated with an increased SEFL efficacy regardless of sex while the roles of the amygdala BDNF transcripts and Gria1 transcript, in either brain region, remained unclear. Altogether, these results prompt future study with modified SEFL into establishing genes driving the observed sex difference, as well as validating the roles of BDNF and Gria1 transcripts, to enhance understanding of PTSD for the sakes of millions struggling to benefit from current treatments and therapies.