Genetic Basis of Mental Illnesses

How is reduced brain activity linked to mental illnesses? The Freiburg neuroscientist Prof. Dr. Marlene Bartos and the molecular medicine specialists Dr. Jonas-Frederic Sauer and Dr. Michael Strüber have discovered that the gene Disrupted-in-schizophrenia 1 (Disc1) reduces the exchange of information between nerve cells. The team hypothesizes that this reduced communication between nerve cells can cause mental illnesses like depression or schizophrenia. Their findings could serve as a basis for new drugs and therapies for such illnesses.

Thoughts and feelings are based on the interaction between nerve cells in the brain, so-called neurons. Chemical messengers are conveyed from one nerve cell to the next, where they trigger electrical signals. A neural network like the brain sends these signals from many nerve cells simultaneously. This is reflected in activity patterns also referred to as brain oscillations. Researchers have observed that these oscillations are reduced in the brains of some individuals with schizophrenia or severe depression. Previous studies indicate that a mutation in the gene Disc1 could be responsible.

A study conducted over several decades on a Scottish family showed that the truncated gene Disc1 caused mental illnesses in members of the family. Researchers triggered this mutation in mice to investigate the consequences of the gene defect and the causes of the illnesses on the mouse models. The Freiburg team confirmed that the mutation of Disc1 leads to behavioral changes resembling depressive behavior. The recorded brain activities of the Disc1 mice were clearly reduced.

To determine the cause of the inhibited brain oscillations, the researchers concentrated on the prelimbic cortex, which is responsible for emotions and motivationally driven behavior. The mouse models exhibited a lower number of a special type of inhibiting neurons known as fast-spiking interneurons. These nerve cells also have a lower number of connections to target cells and have difficulties receiving and sending chemical messengers. This reduces their communication with other neurons. The researchers hypothesize that this is one of the reasons for the reduced brain oscillations. Since the prelimbic cortex integrates the information from various areas of the brain and controls motor behavior, the next step is to determine how this information influences the activity of the prelimbic cortex and thus contributes to depressive behavior.

Originalpublikation:
Jonas-Frederic Sauer, Michael Strüber, Marlene Bartos: Impaired fast-spiking interneuron function in a genetic mouse model of depression. eLife 2015. DOI:

http://dx.doi.org/10.7554/eLife.04979

http://elifesciences.org/content/early/2015/03/03/eLife.04979

Kontakt:
Prof. Dr. Marlene Bartos
Institute of Physiology I / Systemic and Cellular Neurophysiology
University of Freiburg
Phone: +49 (0)761/203-5150
E-Mail: marlene.bartos@physiologie.uni-freiburg.de