Rationale Psychosocial stressors are a well-documented risk
factor for mental illness. Neuroinflammation, in particular elevated
microglial activity, has been proposed to mediate this
association. A number of preclinical studies have investigated
the effect of stress on microglial activity. However, these have
not been systematically reviewed before.
Objectives This study aims to systematically review the effects
of stress on microglia, as indexed by the histological
microglial marker ionised calcium binding adaptor molecule
1 (Iba-1), and consider the implications of these for the role of
stress in the development of mental disorders.
Methods A systematic review was undertaken using predefined
search criteria on PubMed and EMBASE.
Inclusion and data extraction was agreed by two independent
researchers after review of abstracts and full text.
Results Eighteen studies met the inclusion criteria. These used
seven different psychosocial stressors, including chronic restraint,
social isolation and repeated social defeat in gerbils,
mice and/or rats. The hippocampus (11/18 studies) and prefrontal
cortex (13/18 studies) were the most frequently studied
areas. Within the hippocampus, increased Iba-1 levels of between
20 and 200 % were reported by all 11 studies; however,
one study found this to be a duration-dependent effect. Of
those examining the prefrontal cortex, ∼75 % found psychosocial
stress resulted in elevated Iba-1 activity. Elevations
were also consistently seen in the nucleus accumbens, and
under some stress conditions in the amygdala and
paraventricular nucleus.
Conclusions There is consistent evidence that a range of
psychosocial stressors lead to elevated microglial activity
in the hippocampus and good evidence that this is also the
case in other brain regions. These effects were seen with
early-life/prenatal stress, as well as stressors in adulthood.
We consider these findings in terms of the two-hit hypothesis,
which proposes that early-life stress primes microglia,
leading to a potentiated response to subsequent stress. The
implications for understanding the pathoaetiology of mental
disorders and the development of new treatments are
also considered.