FGF-1 triggers pannexin-1 hemichannel opening in spinal astrocytes of rodents and promotes inflammatory responses in acute spinal cord slices

Juan Mauricio Garré, Guang Yang, Feliksas F. Bukauskas, Michael V. L. Bennett

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

We show here that the growth factor FGF-1 is proinflammatory in the spinal cord and explore the inflammatory mechanisms. FGF-1 applied to rat spinal astrocytes in culture initiates calcium signaling and induces secretion of ATP that within minutes increases membrane permeability to ethidium (Etd+) and Ca2+by activatingP2X7 receptors (P2X7Rs) that open pannexin hemichannels (Px1 HCs) that release further ATP; by 7 h treatment, connexin 43 hemichannels (Cx43 HCs) are also opened. In acute mouse spinal cord slices ex vivo, we found that FGF-1 treatment for 1 h increases the percentage of GFAP-positive astrocytes that show enhanced Px1 HC-mediated Etd+ uptake. This response to FGF-1 was not observed in astrocytes in slices of cerebral cortex. FGF-1-induced dye uptake by astrocytes is prevented byBAPTA-AMor a phospholipaseC(PLC) inhibitor. Furthermore, in spinal cord slices,P2X7Rantagonists (BBG and A740003) and Px1HCblockers (10Panx1 and carbenoxolone) prevent the increase in Etd+uptake by astrocytes, whereas Gap19, a selective Cx43HC blocker, has no effect on dye uptake at this time. Microglia are not required for the increase in Etd+ uptake by astrocytes induced by FGF-1, although they are activated by FGF-1 treatment. The morphological signs of microglia activation are inhibited by P2X7R antagonists and 10Panx1 and are associated with elevated levels of proinflammatory cytokines in cord slices treated with FGF-1. The FGF-1 initiated cascade may play an important role in spinal cord inflammation in vivo.

Original languageEnglish (US)
Pages (from-to)4785-4801
Number of pages17
JournalJournal of Neuroscience
Volume36
Issue number17
DOIs
StatePublished - Apr 27 2016

Fingerprint

Fibroblast Growth Factor 1
Astrocytes
Rodentia
Spinal Cord
Microglia
(N-(1-(((cyanoimino)(5-quinolinylamino) methyl) amino)-2,2-dimethylpropyl)-2-(3,4-dimethoxyphenyl)acetamide)
Coloring Agents
Adenosine Triphosphate
Carbenoxolone
Myelitis
Connexin 43
Calcium Signaling
Ethidium
Cerebral Cortex
Permeability
Intercellular Signaling Peptides and Proteins
Cytokines
Membranes

Keywords

  • Astrocyte
  • Fibroblast growth factor
  • Glia
  • Inflammation
  • Microglia
  • Spinal cord

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

FGF-1 triggers pannexin-1 hemichannel opening in spinal astrocytes of rodents and promotes inflammatory responses in acute spinal cord slices. / Garré, Juan Mauricio; Yang, Guang; Bukauskas, Feliksas F.; Bennett, Michael V. L.

In: Journal of Neuroscience, Vol. 36, No. 17, 27.04.2016, p. 4785-4801.

Research output: Contribution to journalArticle

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