A paper by Israeli brain researchers suggests a new direction for studying and treating depression.
Prof. Raz Yirmiya, who heads Hebrew University’s psychoneuroimmunology laboratory, is the senior author of a new paper, “Depression as a microglial disease,” published in the October issue of Trends in Neurosciences.
The paper urges a new focus in depression research away from neurons, the cells that make up the brain’s thinking faculties and allow it to control the body, and toward brain cells called microglia.
About 10 percent of brain cells are microglia, which serve as a kind of infrastructure for the brain, holding neurons in place, passing oxygen and other nutrients to them and fighting brain infections.
Microglia play a special role in repairing brain damage and trauma to neurons, the researchers note.
“Our views on microglia have dramatically changed over the last decade,” Yirmiya said in a Thursday statement by Hebrew University.
“We now know that these cells play a role in the formation and fine-tuning of the connections between neurons [known as synapses] during brain development, as well as in changes [to] these connections throughout life. These roles are important for normal brain and behavioral functions, including pain, mood and cognitive abilities.”
According to Yirmiya, who wrote the paper together with fellow Hebrew University researchers Neta Rimmerman and Ronen Reshef, “Studies in humans, using post-mortem brain tissues or special imaging techniques, as well as studies in animal models of depression, demonstrated that when the structure and function of microglia change, these cells can no longer regulate normal brain and behavior processes and this can lead to depression.”
Major depression “afflicts one in six people at some point in their life,” the university’s statement on the new research noted, and is “the leading global cause of disability – surpassing cardiovascular and respiratory diseases, cancer and HIV/AIDS combined.”
“Progress in the understanding of the biology of depression has been slow,” the researchers note in the paper. New research into the role of malfunctioning microglia could lead to a new push toward finding different and perhaps more effective treatment.
Changes in microglia are found in patients with conditions that correlate with high instances of depression, including “infection, injury, trauma, aging, autoimmune diseases such as multiple sclerosis and neurodegenerative diseases such as Alzheimer’s disease,” the statement explains. Microglia in these conditions take on an “activated” state, growing larger and round while secreting chemicals that lead to inflammation in the brain.
Microglia also change their shape and functioning when exposed to chronic unpredictable psychological stress, which is one of the leading causes of depression. Such conditions have also been found – in research carried out in Yirmiya’s Hebrew University laboratory – to correlate with microglia dying and remaining cells appearing shrunken and degenerated.
Drugs that inhibit overactive microglia or stimulate suppressed microglia may be the key to dramatic new treatments, they argue.
“Prof. Yirmiya’s new research could have a profound impact on the future development of anti-depressant medications. Present drugs do not always have the desired effect on patients, so there is an urgent need to discover novel biological mechanisms and drug targets for diagnosing the root cause of depression and for treating depressed patients appropriately,” the statement read.
New drugs that restore function to diseased microglia, the researchers suggest, may turn out to be as effective as current fast-acting anti-depressants.