Figure 3.

Microglial functional balance is affected by a diversity of environmental factors. Under physiological conditions, microglia interact with the microenvironment through multiple factors (chemokines, cytokines, or/and trophic factors) which modulate its functions in health and disease. As it receives multiple signals from the environment (e.g., brain trauma or injury, infection, alcohol, hormonal imbalance, or omega-3 fatty acid (FA) dietary restrictions), these cells undergo dynamic phenotypic modifications, which convert the homeostatic microglia into reactive microglia. Endocannabinoids derived from the diet act as anti-inflammatory signaling molecules that may restore microglial homeostatic functions. The phenotypic shift towards pro- and anti-inflammatory phenotypes can result in a healing process, whereas an excess of pro- over anti-inflammatory activation can result in pathological outcomes. Normal synaptic pruning and developmental circuitry remodeling depends on homeostatic microglia and, thus, an excess activation through environmental stressors may result in a loss of microglial physiological functions with possible implications on the emergence of pathological conditions such as autism and schizophrenia.