Purinergic Signalling

, Volume 8, Issue 3, pp 629–657

Pathophysiology of astroglial purinergic signalling

  • Heike Franke
  • Alexei Verkhratsky
  • Geoffrey Burnstock
  • Peter Illes
Review

DOI: 10.1007/s11302-012-9300-0

Cite this article as:
Franke, H., Verkhratsky, A., Burnstock, G. et al. Purinergic Signalling (2012) 8: 629. doi:10.1007/s11302-012-9300-0

Abstract

Astrocytes are fundamental for central nervous system (CNS) physiology and are the fulcrum of neurological diseases. Astroglial cells control development of the nervous system, regulate synaptogenesis, maturation, maintenance and plasticity of synapses and are central for nervous system homeostasis. Astroglial reactions determine progression and outcome of many neuropathologies and are critical for regeneration and remodelling of neural circuits following trauma, stroke, ischaemia or neurodegenerative disorders. They secrete multiple neurotransmitters and neurohormones to communicate with neurones, microglia and the vascular walls of capillaries. Signalling through release of ATP is the most widespread mean of communication between astrocytes and other types of neural cells. ATP serves as a fast excitatory neurotransmitter and has pronounced long-term (trophic) roles in cell proliferation, growth, and development. During pathology, ATP is released from damaged cells and acts both as a cytotoxic factor and a proinflammatory mediator, being a universal “danger” signal. In this review, we summarise contemporary knowledge on the role of purinergic receptors (P2Rs) in a variety of diseases in relation to changes of astrocytic functions and nucleotide signalling. We have focussed on the role of the ionotropic P2X and metabotropic P2YRs working alone or in concert to modify the release of neurotransmitters, to activate signalling cascades and to change the expression levels of ion channels and protein kinases. All these effects are of great importance for the initiation, progression and maintenance of astrogliosis–the conserved and ubiquitous glial defensive reaction to CNS pathologies. We highlighted specific aspects of reactive astrogliosis, especially with respect to the involvement of the P2X7 and P2Y1R subtypes. Reactive astrogliosis exerts both beneficial and detrimental effects in a context-specific manner determined by distinct molecular signalling cascades. Understanding the role of purinergic signalling in astrocytes is critical to identifying new therapeutic principles to treat acute and chronic neurological diseases.

Keywords

Astroglia Astrogliosis ATP P2X/Y receptors Neurodegeneration Pathophysiology Purinergic signalling 

Abbreviations

AA

Arachidonic acid

Oligomeric β-amyloid peptide

AC

Adenylate cyclase

AD

Alzheimer’s disease

AKT

Serine-threonine kinase AKT

ALS

Amyotrophic lateral sclerosis

APP

Amyloid precursor protein

ATP

Adenosine 5′-triphosphate

BrdU

5-Bromo-2′-deoxyuridine

[Ca2+]i

Intracellular free calcium concentration

cAMP

Cyclic adenosine-3′,5′-monophosphate

cGMP

Cyclic guanosine-3′,5′-monophosphate

CNS

Central nervous system

COX

Cyclooxygenase

DAG

Diacylglycerol

DRG

Dorsal root ganglion

EGF

Epidermal growth factor

EGFP

Enhanced green fluorescent protein

ERK

Extracellular signal regulated protein kinase

FGF

Fibroblast growth factor

GFAP

Glial fibrillary acidic protein

GSK3

Glycogen synthase kinase 3

IL

Interleukin

InsP3

Inositol (1,4,5)-trisphosphate

IR

Immunoreactivity

JNK

Jun N-terminal kinase

MAPK

Mitogen-activated protein kinase

MCAO

Middle cerebral artery occlusion

MS

Multiple sclerosis

NAc

Nucleus accumbens

NGF

Nerve growth factor

NG2

Chondroitin sulphate proteoglycan

NF-κB

Nuclear factor-κB

NO

Nitric oxide

PD

Parkinson’s disease

PDGF

Platelet-derived growth factor

PGE2

Prostaglandin E2

PKC

Protein kinase C

PI3K

Phosphatidylinositol 3-kinase

PL(A2)

Phospholipase (A2)

PPADS

Pyridoxal-phosphate-6-azophenyl-2′,4′-disulphonic acid

P2R

Purinergic receptor

SAPK

Stress-activated protein kinase

SE

Status epilepticus

STAT3

Signal transducer and activator of transcription 3

TBI

Traumatic brain injury

TNF

Tumor necrosis factor

UTP

Uridine 5′-triphosphate

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Heike Franke
    • 1
  • Alexei Verkhratsky
    • 2
  • Geoffrey Burnstock
    • 3
  • Peter Illes
    • 1
  1. 1.Rudolf Boehm Institute of Pharmacology and ToxicologyUniversity of LeipzigLeipzigGermany
  2. 2.Faculty of Life SciencesThe University of ManchesterManchesterUK
  3. 3.Autonomic Neuroscience CentreRoyal Free and University College Medical SchoolLondonUK

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