The World health Organization calls depression "the leading cause of disability worldwide," causing more years of disability than cancer, HIV/AIDS, and cardiovascular and respiratory diseases combined. In any given year, 5-7% of the world's population experiences a major depressive episode, and one in six people will at some point suffer from the disease.
Hebrew University scientist Prof. Raz Yirmiya: “This suggests new avenues for drug research, in which microglia stimulators could serve as fast-acting antidepressants in some forms of depressive and stress-related conditions.” (Photo courtesy Prof. Yirmiya)
Despite recent progress in understanding depression, scientists still don't understand the biological mechanisms behind it well enough to deliver effective prevention and therapy. One possible reason is that almost all research focuses on the brain's neurons, while the involvement of other brain cells has not been thoroughly examined.
Now researchers at the Hebrew University of Jerusalem have shown that changes in one type of non-neuronal brain cells, called microglia, underlie the depressive symptoms brought on by exposure to chronic stress. In experiments with animals, the researchers were able to demonstrate that compounds that alter the functioning of microglia can serve as novel and efficient antidepressant drugs.
The findings were published in Molecular Psychiatry, the premier scientific journal in psychiatry and one of the leading journals in medicine and the neurosciences. (See Dynamic microglial alterations underlie stress-induced depressive-like behavior and suppressed neurogenesis).
The research was conducted by Prof. Raz Yirmiya, director of the Hebrew University's Psychoneuroimmunology Laboratory, and his doctoral student Tirzah Kreisel, together with researchers at Prof. Yirmiya’s laboratory and at the University of Colorado in Boulder, USA.
The researchers examined the involvement of microglia brain cells in the development of depression following chronic exposure to stress. Comprising roughly 10% of brain cells, microglia are the representatives of the immune system in the brain; but recent studies have shown that these cells are also involved in physiological processes not directly related to infection and injury, including the response to stress.
The researchers mimicked chronic unpredictable stress in humans — a leading causes of depression — by exposing mice to repeated, unpredictable stressful conditions over a period of 5 weeks. The mice developed behavioral and neurological symptoms mirroring those seen in depressed humans, including a reduction in pleasurable activity and in social interaction, as well as reduced generation of new brain cells (neurogenesis) — an important biological marker of depression.
The researchers found that during the first week of stress exposure, microglia cells undergo a phase of proliferation and activation, reflected by increased size and production of specific inflammatory molecules, after which some microglia begin to die. Following the 5 weeks of stress exposure, this phenomenon led to a reduction in the number of microglia, and to a degenerated appearance of some microglia cells, particularly in a specific region of the brain involved in responding to stress.
When the researchers blocked the initial stress-induced activation of microglia with drugs or genetic manipulation, they were able to stop the subsequent microglia cell death and decline, as well as the depressive symptoms and suppressed neurogenesis. However, these treatments were not effective in "depressed" mice, which were already exposed to the 5-weeks stress period and therefore had lower number of microglia. Based on these findings, the investigators treated the "depressed" mice with drugs that stimulated the microglia and increased their number to a normal level.
Prof. Yirmiya said, “We were able to demonstrate that such microglia-stimulating drugs served as effective and fast-acting antidepressants, producing complete recovery of the depressive-like behavioral symptoms, as well as increasing the neurogenesis to normal levels within a few days of treatment. In addition to the clinical importance of these results, our findings provide the first direct evidence that in addition to neurons, disturbances in the functioning of brain microglia cells have a role in causing psychopathology in general, and depression in particular. This suggests new avenues for drug research, in which microglia stimulators could serve as fast-acting antidepressants in some forms of depressive and stress-related conditions.”The Hebrew University’s technology transfer company, Yissum, has applied for a patent for the treatment of some forms of depression by several specific microglia-stimulating drugs.
Dov Smith | Hebrew University
Oxygen can wake up dormant bacteria for antibiotic attacks
08.12.2016 | Penn State
NTU scientists build new ultrasound device using 3-D printing technology
07.12.2016 | Nanyang Technological University
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
08.12.2016 | Materials Sciences
08.12.2016 | Materials Sciences
08.12.2016 | Physics and Astronomy