Microglial-neuronal interactions in synaptic damage and recovery

An understanding of the role of microglial cells in synaptic signaling is still elusive, but the neuron-microglia relationship may have important ramifications for brain plasticity and injury. This review summarizes current knowledge and theories concerning microglial-neuronal signaling, both in terms of neuron-to-microglia signals that cause activation and microglia-to-neuron signals that affect neuronal response to injury. Microglial activation in the brain involves a stereotypical pattern of changes including proliferation and migration to sites of neuronal activity or injury, increased or de novo expression of immunomodulators including cytokines and growth factors, and the full transformation into brain-resident phagocytes capable of clearing damaged cells and debris. The factors released from neurons that elicit such phenotypical and functional alterations are not well known but may include cytokines, oxidized lipids, and/or neurotransmitters. Once activated, microglia can promote neuronal injury through the release of low-molecular-weight neurotoxins and support neuronal recovery through the release of growth factors and the isolation/removal of damaged neurons and myelin debris. Because microglia respond quickly to neuronal damage and have robust effects on neurons, astrocytes, and oligodendrocytes, microglial cells could play potentially key roles in orchestrating the multicell cascade that follows synaptic plasticity and damage.