Brain Res Rev
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The classical view of glial cells as simple supportive cells for neurons is being replaced by a new vision in which glial cells are active elements involved in the physiology of the nervous system. This new vision is based on the fact that astrocytes, a subtype of glial cells in the CNS, are stimulated by synaptically released neurotransmitters, which increase the astrocyte Ca(2+) levels and stimulate the release of gliotransmitters that regulate synaptic efficacy and plasticity. ⋯ Hence, astrocytes have been revealed as integral elements involved in the synaptic physiology, therefore contributing to the processing, transfer and storage of information by the nervous system. Reciprocal communication between astrocytes and neurons is therefore part of the intercellular signaling processes involved in brain function.
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The major glial population of the brain is constituted by astroglia. Highly branched and ramified protoplasmic astrocytes are the predominant form in grey matter and are found in almost all regions of the central nervous system. In cerebellum and retina, there two forms of elongated radial glia exist (Bergmann glia and Müller cells, respectively) that share many features with the protoplasmic astrocytes in respect to their perisynaptic association. ⋯ After signal integration, they can also modulate synaptic transmission, thereby contributing to neural plasticity. Despite their importance, the mechanisms that (1) target astroglial processes toward pre- and postsynaptic compartments and (2) control the interaction during plastic events of the brain such as learning or injury are poorly understood. This review will summarize our current knowledge and highlight some open questions.
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A growing body of evidence indicates that extracellular nucleotides play important roles in the regulation of neuronal and glial functions in the nervous system through P2 purinoceptors. P2 purinoceptors are divided into two families, ionotropic receptors (P2X) and metabotropic receptors (P2Y). P2X receptors (seven types; P2X1-P2X7) contain intrinsic pores that open by binding with ATP, and P2Y receptors (eight types; P2Y1, 2, 4, 6, 11, 12, 13 and 14) are activated by nucleotides and couple to intracellular second-messenger systems through heterotrimeric G-proteins. ⋯ These activated microglia upregulate expression of P2X/Y receptors (e.g., P2X4 and P2Y12). Importantly, pharmacological, molecular and genetic manipulations of the function or expression of these microglial molecules strongly suppress neuropathic pain. We expect that further investigation to determine how ATP signaling via P2X receptors participates in the pathogenesis of chronic pain will lead to a better understanding of the molecular mechanisms of pathological pain and provide clues for the development of new therapeutic drugs.