Effects of TCF7L2 on Nicotine Addiction and Glucose Metabolism in Nicotine-Dependent Rat Strains
Project no. 28522 · Status: Kapanmış (Yayın bekleniyor) · 2023
Summary
<p>When we look at cigarette consumption in recent years, it ranks first among the causes of preventable deaths. Worldwide, it is known that more than five million people die from smoking-related diseases every year. It is known that the main substance in cigarettes that causes addiction is nicotine, which is effective as a psychostimulant in the brain, also stimulates the reward system, and finally, it is known to reduce stress and anxiety. It has been shown in many recent publications that hereditary characteristics are important in nicotine addiction. The project to establish nicotine-preferring (NTE) rat strains within the Ege University, Faculty of Medicine, Department of Physiology has been ongoing since 2006. These rat strains appear to have an 80% higher nicotine preference than naive control rats. In addition, the effect of nicotine on glucose metabolism has been shown in studies. These studies in the literature indicate that these effects may be related to TCF7L2, a transcription factor most commonly found in the habenular region of our brain. Decreasing the expression of GSK-3β, located in the upstream region of TCF7L2, increases the expression of this transcription factor. Increasing the expression of TCF7L2 increases the release of GLP-1 in the downstream region. Based on the potential of increased TCF7L2 expression in nicotine addiction to end nicotine addiction and its neuroprotective effects for various neurological and metabolic diseases, this study was planned to evaluate the potential of TCF7L2 transcription factor in the experimental model of nicotine addiction. Finally, this planned study raises the question of whether and how TCF7L2 can be targeted in the fight against nicotine addiction, diabetes, and the neurodegenerative diseases they cause. On the other hand, there are not enough studies examining TCF7L2's effects on nicotine addiction and the changes in blood glucose levels caused by it in terms of metabolic disorders.</p><p>Therefore, in our study in the nicotine-dependent rat model; especially the medial habenula (mHb) and inter peduncular nucleus (IPN) located in the epithalamus from the midbrain region; together with the</p><p>prefrontal cortex (PFC), septum, dorsalstriatum (DST), nucleus accumbens (NAc), amygdala (AMG), hippocampus (HIP), medial hypothalamic area (MHA), Ventral Tegmental Area (VTA), paraventricular nucleus of the hypothalamus (PVN), Arcuate nucleus (ARC), lateral hypothalamic area (LHA) and the pancreas were aimed to be analyzed with molecular biological methods. It has been also planned to support this molecular biological study with findings from behavioral tests applied to experimental animals.</p><p>In the proposed project, in order to see the effects of nicotine use blood will be taken twice in total, at the beginning and at the end of the study, and biochemical analyzes will be carried out. In addition, it is planned to investigate the changes in GLP1-R, TCF7L2, GSK3B, BDNF and CHRNA7 mRNA expression levels in the determined brain regions and pancreas of rats to examine the effects of nicotine at the molecular level.</p>