In vivo characterization of functional states of cortical microglia during peripheral inflammation
Karin Riester1, Bianca Brawek1, Daria Savitska1
1Institute of Physiology, Department of Neurophysiology, Eberhard Karls University Tübingen, Tübingen, Germany.
Abstract:
Peripheral inflammation is known to trigger a mirror inflammatory response in the brain, involving brain's innate immune cells - microglia. However, the functional phenotypes, which these cells adopt in the course of peripheral inflammation, remain obscure. In vivo two-photon imaging of microglial Ca2+ signaling as well as process motility reveals two distinct functional states of cortical microglia during a lipopolysaccharide-induced peripheral inflammation: an early "sensor state" characterized by dramatically increased intracellular Ca2+ signaling but ramified morphology and a later "effector state" characterized by slow normalization of intracellular Ca2+ signaling but hypertrophic morphology, substantial IL-1β production in a subset of cells as well as increased velocity of directed process extension and loss of coordination between individual processes. Thus, lipopolysaccharide-induced microglial Ca2+ signaling might represent the central element connecting receptive and executive functions of microglia.
Insights
Peripheral inflammation induces two distinct microglial states in the brain. Microglia shift from a "sensor state" with high calcium signaling to an "effector state" with altered morphology and function.
Area of Science:
- Neuroimmunology
- Cellular Neuroscience
Background:
- Peripheral inflammation triggers neuroinflammation involving microglia, the brain's innate immune cells.
- The specific functional changes microglia undergo during peripheral inflammation are not well understood.
Purpose of the Study:
- To investigate the dynamic functional phenotypes of cortical microglia during lipopolysaccharide-induced peripheral inflammation.
- To elucidate the role of microglial calcium (Ca2+) signaling in mediating these functional states.
Main Methods:
- In vivo two-photon imaging was used to monitor microglial Ca2+ signaling and process dynamics.
- Lipopolysaccharide (LPS) was administered to induce peripheral inflammation in a mouse model.
Main Results:
- Two distinct microglial states were identified: an early "sensor state" (high Ca2+ signaling, ramified morphology) and a later "effector state" (normalized Ca2+ signaling, hypertrophic morphology, IL-1β production, directed process extension).
- Microglial Ca2+ signaling dynamics correlated with morphological and functional changes, suggesting a link between receptive and executive functions.
Conclusions:
- Microglia exhibit distinct functional states during peripheral inflammation, transitioning from sensing to effector roles.
- Microglial Ca2+ signaling is a key mediator connecting the sensing and effector functions of microglia in response to inflammatory stimuli.
