Purine Signaling and Microglial Wrapping

Adv Exp Med Biol. 2016:949:147-165. doi: 10.1007/978-3-319-40764-7_7.

Abstract

Microglial cells are highly dynamic cells with processes continuously moving to survey the surrounding territory. Microglia possess a broad variety of surface receptors and subtle changes in their microenvironment cause microglial cell processes to extend, retract, and interact with neuronal synaptic contacts. When the nervous system is disturbed, microglia activate, proliferate, and migrate to sites of injury in response to alert signals. Released nucleotides like ATP and UTP are among the wide range of molecules promoting microglial activation and guiding their migration and phagocytic function. The increased concentration of nucleotides in the extracellular space could be involved in the microglial wrapping found around injured neurons in various pathological conditions, especially after peripheral axotomy. Microglial wrappings isolate injured neurons from synaptic inputs and facilitate the molecular dialog between endangered or injured neurons and activated microglia. Astrocytes may also participate in neuronal ensheathment. Degradation of ATP by microglial ecto-nucleotidases and the expression of various purine receptors might be decisive in regulating the function of enwrapping glial cells and in determining the fate of damaged neurons, which may die or may regenerate their axons and survive.

Keywords: ATP; Adenosine; Axotomy; CD39; Microglial migration; Nerve injury; Neuronal degeneration; Phagocytosis; Purine receptors; ‘Eat-me’ signals.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Animals
  • Axotomy
  • Cell Communication
  • Cell Movement / physiology
  • Cytokines / genetics
  • Cytokines / metabolism
  • Gene Expression
  • Humans
  • Microglia / cytology
  • Microglia / physiology*
  • Motor Neurons / cytology
  • Motor Neurons / physiology*
  • Nerve Regeneration / physiology
  • Neurotransmitter Agents / genetics
  • Neurotransmitter Agents / metabolism
  • Phagocytosis / physiology
  • Receptors, Purinergic / genetics
  • Receptors, Purinergic / metabolism*
  • Signal Transduction
  • Synapses / physiology*
  • Uridine Triphosphate / metabolism*

Substances

  • Cytokines
  • Neurotransmitter Agents
  • Receptors, Purinergic
  • Adenosine Triphosphate
  • Uridine Triphosphate