Role of Glutamate Transporter EAAT2 in Stress-Induced Depression
Loading...
Date
2016-05
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
The Ohio State University
Abstract
To date, drug treatments for Major Depressive Disorder (MDD) have focused mainly on monoamine neurotransmitters such as noradrenaline and serotonin. However, monoaminergic antidepressants require long therapeutic latency and do not work for some subpopulations of patients. Therefore there is a pressing need to develop more effective means for treating MDD. Several lines of evidence indicate that dysfunction of the glutamatergic system plays a critical role in the pathogenesis of depression. Repeated stress results in an increase in extracellular glutamate and the overall dyshomeostasis of the glutamatergic system, which may lead to MDD. Glutamate transporter EAAT2 is primarily expressed in astrocytes and is mainly responsible for glutamate homeostasis in the forebrain. This study seeks to determine if increased EAAT2 expression could reduce susceptibility to depression due to unpredictable chronic mild stress. EAAT2 transgenic mice, which express ~ 2 fold more EAAT2 protein, were used in this study. EAAT2 mice and their wild-type littermates undergo a month of unpredictable chronic stress. During this month, weekly behavioral analyses including sucrose preference tests were performed to analyze the extent of depression-like symptoms. After one month of chronic stress, other behavioral tests including open field, novelty-suppressed feeding, and forced swim test were conducted. Following behavioral tests, brains and adrenal glands were harvested to determine the weights of the adrenal glands and EAAT2 protein expression in the prefrontal cortex by Western blot analysis. Results show no significant differences in all behavioral tests except for coat state assessment. There were also no significant differences between testing conditions in the weight of adrenal glands. EAAT2 expression was not significantly different between conditions within each mouse strain. This evidence suggests that we were not successful in producing depression-like symptomology with the unpredictable chronic mild stress model. Proposed future studies would use a modified unpredictable mild stress model with different stressors for increased durations as well as a different mouse strain that would be treated with a small molecule compound, LDN/OSU-0212320, which our lab has shown in previous experiments to increase the expression of EAAT2.
Description
Keywords
EAAT2, Glutamate, Depression, Neuroscience, UCMS