depression is the most significant cause of disability around the world, yet
scientists still don’t understand the biological mechanisms behind it well
enough to prevent or treat it adequately – partly because most research focuses
on neurons in the brain and not other cells in the cerebellum.
A study by
researchers at the Hebrew University of Jerusalem have found that changes in one
type of non-neuronal brain cells – microglia – underlie the depressive symptoms
brought on by exposure to chronic stress.
Their findings, published in
the prestigious scientific journal Molecular Psychiatry, showed that in
experiments with animals, compounds that alter the functioning of microglia can
serve as efficient anti-depressant drugs.
Yissum, the university’s
technology transfer company, has applied for a patent for the treatment of some
forms of depression by several specific microglia- stimulating
Prof. Raz Yirmiya, director of the Hebrew University’s
psychoneuroimmunology lab, and doctoral student Tirzah Kreisel, together with
researchers at Yirmiya’s laboratory and at the University of Colorado in Boulder
conducted the research.
The researchers examined in mice the involvement
of microglia brain cells in the development of depression, following chronic
exposure to stress. Comprising a 10th 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.
team 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
Following five 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.
Yirmiya explained: “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 anti-depressants in some forms of depressive and stress-related
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