Altering adult Hippocampal Neurogenesis in the dentate gyrus through varying glucocorticoid receptor concentrations

Abstract

Adult Hippocampal Neurogenesis, short for AHN, is an essential yet foundational process of producing new nerve cells in the dentate gyrus of the hippocampus. It is a fact that increasing AHN will enhance peoples ability to learn, memorize, regulate mood, etc. Therefore, scientists strive to pursue the factors which influence AHN. Until now, research had proved that GR activity is associated with the degree of AHN. Additionally, a high GR activity will potentially reduce the level of ANH and an optimal level of GR activity will create the optimized level of AHN. Consequently, how a low level of GR activity will possibly influence AHN will be examined in this paper. For Experiment 1, the GR antagonist reduces the GR activity in 8-year-old male mice: C57BL/6 and BrdU highlights the newly generated neurons in the dentate gyrus. As an ideal result compared to the control group, low GR activity will lead to a decrease in the AHN. For Experiment 2, 3 minor experiments will be constructed to test the GR activity and AHN of the mice in 3 different conditions (low, controllable, and uncontrollable stress). And Nanobit Assay that is separately attached to the GR and the ligands will present fluorescent when combined. Additionally, the method of CRISPR-CAS9 is used to knock down either GR or GR when the other one is measured, and BrdU is also used to light up the neurons to measure the degree of AHN. The ideal result will present a number greater than 1 for the ratio between GR/GR and AHN decreases for the low-stress group and uncontrollable-stress group. Oppositely, the ratio will be smaller than 1 for the controllable stress group, meaning AHN increases. Conclusively, the output will demonstrate a reversed U shape with the x-axis being the level of GR activity and the y-axis presenting the level of AHN. Despite the experiments that have proceeded on mice, the significance of them is people will have certain references to the influences of AHN to prevent those conditions or stress which will negatively affect AHN.