Understanding Cardiovascular Disease in Mental Health/Stress Disorder
Abstract
Mental health disorder increases risk for cardiovascular disease (CVD). However, the mechanisms are poorly understood. Purpose: Our goal is to investigate the cause-effect relationship between comorbid depression and cardiac pathology and dysfunction. Scope: To test the hypothesis that depression alters neurotrophins and receptor interactions leading to cardiac pathophysiological changes and dysfunction. In this reporting period (May 1, 2023 to April 30, 2024), we have obtained UAB-IACUC and UAB-Environmental Health and Safety approvals and subsequently obtained OHARO approval. We have procured breeder mouse, p75NTR global knockout mice from Jackson laboratory and p75NTR flox/flox mice from Indiana University. We are in the process of breeding and expanding the mouse colonies to obtain a critical number of mice to test our hypotheses. Due to technical challenges in obtaining homozygous knockout mice (described in section 5 of this report), we are continuing to breed the mice and we have drawn several contingency plans. Next, we performed initial set of in vitro experiments in cell culture system to determine the effect of loss of P75NTR on cell death. The siRNA transfections (to delete p75NTR) did not reveal efficient knockdown. Therefore, alternatively, we are preparing plasmid for CRISPR-Cas9 method of gene deletion and testing the effect p75NTR loss on cell death and proliferation. These steps will ensure preparation for experiments proposed in the next reporting period.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2024
- Accession Number
- AD1229030
Entities
People
- Prasanna Krishnamurthy
Organizations
- University of Alabama