Apc Mutant Fare Modelinde Azaltılmış Bdnf Ekspresyonunun İntestinal Tümör Gelişimi Üzerine Etkilerinin Araştırılması

Abstract

Gök, A., Effects of Reduced Bdnf Expression on Intestinal Tumor Development in Apc Mutant Mouse Model, Hacettepe University Graduate School of Health Sciences Department of Stem Cell Sciences Doctor of Philosophy Thesis, Ankara, 2023. A mutation in adenomatous polyposis coli (Apc) tumor suppressor gene, which negatively regulates Wnt signaling, is the most common mutation in colon cancers. Brain-derived neurotrophic factor (Bdnf), one of the genes regulated by the Wnt signaling pathway, is expressed at high levels in many tumor tissues such as colorectal cancers. In this thesis study; It was aimed to investigate the effects of decreased Bdnf expression on intestinal tumor development in Apc mutant mice. In this context; we followed up Apc+/-, Bdnf+/-, Apc+/-Bdnf+/- and wild-type mouse experimental and control groups for 36 weeks and investigated the effects of Bdnf mutation on Apc mutant mice phenotypically and molecularly. When the experiments are finished; compared to Apc+/- and wild-type mice, while half of the group had normal body weight, a significant weight gain was observed in the other half in Bdnf+/- female and male mice. A similar trend of weight gain occurred in Apc+/- Bdnf+/- mice. Apc+/- Bdnf+/- mice did not show any disease phenotypes such as anemia, weight loss, discolored fur, or altered posture during the first 6 months compared to Apc+/- mice. Survival times of Apc+/- Bdnf+/- mice increased by approximately 2 months compared to Apc+/- mice. While it slightly decreased the number of polyps in the small intestine of Apc+/- Bdnf+/- mice, it significantly increased the number of polyps in the colon of Apc+/- Bdnf+/- mice. Bdnf, Trk B, beta catenin and Lgr5 gene expressions and mature and immature Bdnf and beta catenin protein levels were decreased in tumors of Apc+/- Bdnf+/- mice compared to Apc+/- mice, so it was thought that stem cell dynamics might also change. As a result of this study; we think that BDNF may be an important candidate molecule for the treatment of intestinal tumors starting with Apc mutation.