Microglia are the resident immune cells of the adult brain that become activated in response to pathogen- or damage-associated stimuli. The acute inflammatory response to injury, stress, or infection comprises the release of cytokines and phagocytosis of damaged cells. Accumulating evidence indicates chronic microglia-mediated inflammation in diseases of the central nervous system, most notably neurodegenerative disorders, that is associated with disease progression. To understand microglia function in pathology, knowledge of microglia communication with their surroundings during normal state and the release of neurotrophins and growth factors in order to maintain homeostasis of neural circuits is of importance. Recent evidence shows that microglia interact with serotonin, the neurotransmitter crucially involved in adult neurogenesis, and known for its role in antidepressant action. In this chapter, we illustrate how microglia contribute to neuroplasticity of the hippocampus and interact with local factors, e.g., BDNF, and external stimuli that promote neurogenesis. We summarize the recent findings on the role of various receptors in microglia-mediated neurotransmission and particularly focus on microglia’s response to serotonin signaling. We review microglia function in neuroinflammation and neurodegeneration and discuss their novel role in antidepressant mechanisms. This synopsis sheds light on microglia in healthy brain and pathology that involves serotonin and may be a potential therapeutic model by which microglia play a crucial role in the maintenance of mood.
Neuroinflammation causes morphological and functional changes in the nervous tissue and it can be triggered by different kind of stressors. Progress of neuroinflammation as a result of post-traumatic stress disorder (PTSD) is associated with morphological changes in neurons and glial cells, as well as activation of microglia, however the exact molecular mechanisms of these changes are still unknown. In this review we discuss the connections between endocrine, immune and limbic systems during stress, the contributions of each system, the role of blood-brain barrier, as well as current methods and approaches in studying neuroinflammation.
Stress plays an important role in the pathogenesis of anxiety
and depressive disorders. Neuroinflammation is considered as one
of the mechanisms by which stress alters the molecular and cellular
plasticity in the nervous tissue and thus entails CNS dysfunction.
The contribution of genetically determined features of the nervous
system to the development of post-stress neuroinflammation has not
been sufficiently studied. In this study, the dynamics of post-stress changes
in mRNA levels of the
il-1
β
and
tnf
genes encoding proinflammatory
cytokines interleukin-1 beta (IL-1β) and tumor necrosis factor (TNF)
were evaluated in the blood and brain of two rat strains with high
and low excitability thresholds of the nervous system (HT and LT, respectively).
Changes in IL-1β and TNF mRNA levels were assessed by real-time
PCR 24 h, 7, 24 and 60 days after long-term long-term emotional
and painful stress in the blood and three brain structures involved
in the development of post-stress pathology (prefrontal cortex,
hippocampus, amygdala). In highly excitable LT rats, IL-1β mRNA
level in the hippocampus and amygdala increased compared to the
control 24 days after stress termination, while in low-excitable
HT animals, an increase in the level of IL-1β mRNA was only detected
in the hippocampus at the same time point. TNF mRNA level did not
change in any of the rat strains at any of the post-stress time points.
Genetically determined excitability of the nervous system is a promising
marker of individual stress vulnerability, as manifested in post-stress
disorders associated with developmental and time-course features
of neuroinflammation.
An enriched environment stimulates adult hippocampal plasticity, but the exact cellular and molecular mechanisms are complex, and thus a matter of debate. We studied the behavior and hippocampal neurogenesis in adult male and female Wistar rats that were housed in an enriched environment (EE) for two months. Both EE males and females performed better than control animals in a Barnes maze, meaning that EE enhances spatial memory. However, the expression levels of neurogenesis markers KI67, DCX, Nestin, and Syn1 increased only in EE females, while in EE males only KI67 and BDNF were higher than in the corresponding control. The number of DCX+ neurons on brain slices increased in the dentate gyrus of EE females only, i.e., the level of adult hippocampal neurogenesis was increased in female but not in male rats. The level of anti-inflammatory IL-10 and signaling pathway components was upregulated in EE females. Of 84 miRNAs tested, in the hippocampi of EE female rats we detected upregulation in the expression levels of 12 miRNAs related to neuronal differentiation and morphogenesis, while in EE males four miRNAs were upregulated and involved in the regulation of cell proliferation/differentiation, and one was downregulated and associated with the stimulation of proliferation. Taken altogether, our results point to sex-specific differences in adult hippocampal plasticity, IL-10 expression, and miRNA profiles induced by an enriched environment.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.