Reduced Microglial Activity Affects Fight Against Foreign Substances in Major Depressive Disorder

Researchers from the Netherlands found that downregulation of microglial activity is associated with the development of major depressive disorder. In particular, they revealed a specific decrease in the fight against foreign particles, but only in gray matter tissues. Results of analysis and profiling of gray and white matter microglial gene expression published V Biological Psychiatry.

Microglia – Immune cells of the central nervous system that protect neurons and remove the products of destruction of nervous tissue. These cells are also involved in the inflammatory response and are able to destroy synapses – the place of signal transmission between neurons – to suppress their excessive activity.

Past Research revealed changes in microglia associated with the development of schizophrenia, autism spectrum disorder, major depressive disorder and bipolar disorder. Gene expression profiling, one type of study of genetic markers of diseases, can help to understand in more detail the features of the work of microglia. So, earlier researchers from the USA found similar expression profiles in common mental disorders, including depression. However, it is not clear whether such changes in microglia are beneficial or harmful.

Researchers from the Netherlands, with the participation of Karel WF Scheepstra from the Netherlands Institute of Neurosciences, decided to study the gene expression of microglial cells in the brains of patients with major depressive disorder and healthy people who signed an agreement for organ donation for research during their lifetime.

The authors extracted microglia from the gray matter of the occipital cortex and the white matter of the corpus callosum. They then isolated and sequenced RNA to obtain the primary structure of RNA molecules in order to compose gene expression profiles.

In the microglia of the gray matter of patients with depression, the researchers found differences in comparison with the material of healthy people for 92 genes: 81 of them showed lower expression, and 11 showed higher expression. In white matter microglia, no such differences were found.

Next, the authors checked the activation pathways of which functions include genes with suppressed expression. Most of all, the pathways associated with the phagocytic activity of microglia, that is, with the suppression and destruction of foreign particles, and complement systemwhich is also involved in the immune response.

Analysis of gene co-expression identified three depression-specific clusters. The most significant was the cluster responsible for vesicular organization, intracellular transport and macroautophagy.

The authors note that they found no evidence of an association of major depressive disorder with an increased immune response, which means that the common idea that inflammation is associated with depression may be false.

Earlier, we talked about how microglia and astrocytes remove the remnants of dead neurons, and also that microglia can destroy inhibitory synapses during development.