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Title: Brain Drain: Investigating the Role of Chronic Stress on Mitochondrial Functioning in the Mouse Brain
Authors: Devraj, Varun
Advisors: Notterman, Daniel
Department: Molecular Biology
Certificate Program: Global Health and Health Policy Program
Class Year: 2023
Abstract: Chronic stress can lead to adverse health effects, including increased rate of aging, brain damage, and cardiovascular disease. Physiologically, chronic stress is caused by a dysregulation of the HPA (hypothalamic-pituitary-adrenal) axis and its downstream effects on the body. Based on their central role in synthesizing ATP and producing harmful oxidative species, research has identified mitochondria as being an important organelle in contributing to the stress response. However, the precise impacts of chronic stress in the brain on physiologically relevant mitochondrial parameters, such as respiratory capacity and mitochondrial membrane potential, are unknown. In this thesis, using brain tissues from a chronic restraint stress (CRS) mouse model, I first characterized mitochondrial function with both a fluorescent probe of mitochondrial membrane potential and by measuring the oxygen consumption of coupled, respiring mitochondria. While other respiratory parameters were unchanged between CRS and control mice, maximal ATP-linked respiration in the cerebellum of CRS mice was significantly decreased. In addition, proteomic analysis of isolated mitochondria was conducted in order to elucidate whether chronic stress alters protein pathways associated with mitochondrial dynamics and functioning. Indeed, differential, brain region-specific expression of respiratory proteins and mitochondria-linked protein pathways was seen in CRS mice. Together, my results present preliminary evidence that chronic stress alters mitochondria-specific pathways in the brain and that mitochondria also have regional brain differences in their response to chronic stressors. These results have implications for more holistic studies into the physiological effects of chronic stress on an organism’s brain and body.
Type of Material: Princeton University Senior Theses
Language: en
Appears in Collections:Molecular Biology, 1954-2024
Global Health and Health Policy Program, 2017-2023

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