The effects of brain-derived insulin loss on adult neurogenesis in aged male and female Ins2 knockout mice
department or school: Medicine, Faculty of
data provider: DSpace
degree campus: UBCV
creator: Baehring, Stella
issued: 2022-12-12T22:49:35Z
issued: 2022
related degree: Master of Science - MSc
degree grantor: University of British Columbia
description: Insulin resistance in the brain is associated with Alzheimer’s disease, the most common form of dementia with women being more affected than men. Diabetes is a metabolic disorder signified by dysfunctional insulin release and action, and it is a risk factor for Alzheimer’s Disease. Interestingly, administration of insulin to the brain is an effective experimental treatment to improve learning and memory impairments in Alzheimer’s Disease patients. This suggests an important role of insulin action local to the brain. Increasingly more research reports that insulin can be synthesized in the hippocampus, the brain region responsible for learning and memory, and one of the only areas in which new neurons can form throughout adulthood. However, not much is known about how brain-derived insulin effects adult neurogenesis and what factors modulate its expression. This study aimed to confirm insulin production in the hippocampus, assess its modulation by diet and exercise, and identify how brain-derived insulin loss affects adult neurogenesis in female and male mice. I hypothesized that insulin expression is most abundant in the hippocampus, that a high carbohydrate diet decreases insulin expression while exercise increases its expression, and that brain-derived insulin loss decreases adult neurogenesis. To examine these aims I utilized a genetically engineered mouse model with deletion of the Ins2 gene (expressed in the brain) while leaving the Ins1 gene (expressed only in the pancreas), and thus normal glucose homeostasis, intact. In line with my prediction, Ins2 mRNA was high in the hippocampus compared to other regions. Ins2 mRNA was expressed at higher levels in hippocampi of females than males. Contrary to my prediction, Ins2 expression was higher in females eating a high carbohydrate diet and exercise blunted this effect. Surprisingly, the deletion of Ins2 alleles led to increased cell proliferation and this effect was sexually dimorphic. Overall, these results sugge…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/83402
note: THE EFFECTS OF BRAIN-DERIVED INSULIN LOSS ON ADULT NEUROGENSIS IN ADGED MALE AND FEMALE Ins2 KNOCKOUT MICE by Stella Baehring B.A., The University of British Columbia, 2018 Cert. Ed., Academy of Social Pedagogy, 2012 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Cell and Developmental Biology) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) December 2022 © Stella Baehring, 2022 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, a thesis entitled: THE EFFECTS OF BRAIN-DERIVED INSULIN LOSS ON ADULT NEUROGENSIS IN ADGED MALE AND FEMALE Ins2 KNOCKOUT MICE submitted by Stella Baehring in partial fulfillment of the requirements for the degree of Master of Science in Cell and Developmental Biology Examining Committee: James D Johnson, PhD, Professor, Cellular and Physiological Sciences, UBC Supervisor Jason S Snyder, PhD, Associate Professor, Department of Psychology, UBC Supervisory Committee Member Shernaz X Bamji, PhD, Professor, Cellular Physiological Sciences, UBC Supervisory Committee Member Liisa AM Galea, PhD, Professor, Department of Psychology, UBC Additional Examiner Additional Supervisory Committee Members: Kiran K Soma, PhD, Professor, Department of Psychology, UBC Supervisory Committee Member iii Abstract Insulin resistance in the brain is associated with Alzheimer’s disease, the most common form of dementia with women being more affected than men. Diabetes is a metabolic disorder signified by dysfunctional insulin release and action, and it is a risk factor for Alzheimer’s Disease. Interestingly, administration of insulin to the brain is an effective experimental treatment to improve learning and memory impairments in Alzheimer’s Disease patients. This suggests an important role of insulin action local to the brain. Increasingly more research reports that insulin can b…
has type: Thesis/Dissertation
date issued: 2023-05
is shown at: 10.14288/1.0422493
language: eng
degree discipline: Cell and Developmental Biology
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
contributor: Johnson, James D.
type: Text
identifier URI: http://hdl.handle.net/2429/83402