Purines in neurite growth and astroglia activation

Neuropharmacology. 2016 May:104:255-71. doi: 10.1016/j.neuropharm.2015.10.022. Epub 2015 Oct 21.

Abstract

The mammalian nervous system is a complex, functional network of neurons, consisting of local and long-range connections. Neuronal growth is highly coordinated by a variety of extracellular and intracellular signaling molecules. Purines turned out to be an essential component of these processes. Here, we review the current knowledge about the involvement of purinergic signaling in the regulation of neuronal development. We particularly focus on its role in neuritogenesis: the formation and extension of neurites. In the course of maturation mammals generally lose their ability to regenerate the central nervous system (CNS) e.g. after traumatic brain injury; although, spontaneous regeneration still occurs in the peripheral nervous system (PNS). Thus, it is crucial to translate the knowledge about CNS development and PNS regeneration into novel approaches to enable neurons of the mature CNS to regenerate. In this context we give a general overview of growth-inhibitory and growth-stimulatory factors and mechanisms involved in neurite growth. With regard to neuronal growth, astrocytes are an important cell population. They provide structural and metabolic support to neurons and actively participate in brain signaling. Astrocytes respond to injury with beneficial or detrimental reactions with regard to axonal growth. In this review we present the current knowledge of purines in these glial functions. Moreover, we discuss organotypic brain slice co-cultures as a model which retains neuron-glia interactions, and further presents at once a model for CNS development and regeneration. In summary, the purinergic system is a pivotal factor in neuronal development and in the response to injury. This article is part of the Special Issue entitled 'Purines in Neurodegeneration and Neuroregeneration'.

Keywords: Astrogliosis; Axon growth; Glial scar; Neurite growth; Neuronal development; P2 receptors; Purines; Regeneration.

Publication types

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

MeSH terms

  • Animals
  • Astrocytes / metabolism
  • Astrocytes / physiology*
  • Brain Injuries, Traumatic / metabolism
  • Central Nervous System / growth & development*
  • Central Nervous System / metabolism
  • Gliosis / metabolism
  • Humans
  • Nerve Regeneration*
  • Neurites / metabolism
  • Neurites / physiology*
  • Peripheral Nervous System / growth & development*
  • Peripheral Nervous System / metabolism
  • Purines / metabolism*
  • Receptors, Purinergic P2X / metabolism
  • Receptors, Purinergic P2X / physiology
  • Receptors, Purinergic P2Y / metabolism
  • Receptors, Purinergic P2Y / physiology

Substances

  • Purines
  • Receptors, Purinergic P2X
  • Receptors, Purinergic P2Y