Are major depressive disorder caused by abnormal glutamate regulation by astrocytes?

Major depressive disorder is characterized by sadness, anhedonia, and impaired cognitive function and is a leading cause of disability worldwide with one in five people experiencing at least one depressive episode in their lifetime.

Acute stress responses serve to adapt to threatening situations by enhancing brain transmission in cortical and hippocampal areas creating appropriate behavioral responses. However, exposure to chronic stress can trigger detrimental amounts of brain activity leading to reduced brain transmission and increased risk of developing major depressive disorder.

In this master project, you will test if brain cells known as astrocytes serve as brakes on stress-induced brain transmission by regulating the amount of excitation and inhibition in the brain. Furthermore, you will determine if exposure to chronic stress causes astrocytic dysfunction thereby lifting the brake and accelerating the excitotoxic effects of hyperactive brain transmission.

The proposed study will use genetically encoded sensors to perform deep brain imaging in freely moving mice exposed to a social defeat depression paradigm (figure). The finding may pin-point astrocytes as a novel player in stress responses thereby identifying new targets for treatment of major depressive disorder.

Schematic of experiment

Our center (https://ctn.ku.dk/) is led by professor Maiken Nedergaard and Steve Goldman and is situated at the Panum Institute. It is a dynamic international research environment with more than 40 people working on various projects centered on glial cells in the brain. The center is very resourceful with a range of different techniques and methods available.

If you want to learn more, feel free to contact assistant professor, Celia Kjærby, at Center for Translational Neuromedicine, at celia.kjaerby@sund.ku.dk.