P2 receptor antagonist trinitrophenyl-adenosine-triphosphate protects hippocampus from oxygen and glucose deprivation cell death

Fabio Cavaliere, Susanna Amadio, Klaus Dinkel, Klaus G. Reymann, Cinzia Volonté

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Abstract

In this work, we mainly used the organotypic model of rat hippocampus to demonstrate the protective role of the P2 receptor antagonist trinitrophenyl-adenosine-triphosphate (TNP-ATP) during oxygen/glucose deprivation. Among the P2X receptors that TNP-ATP specifically blocks, mainly P2X1 seems to be involved in the processes of cell damage after oxygen/glucose deprivation. P2X1 receptor is strongly and transiently up-regulated in 24 h after an ischemic insult on structures likely corresponding to mossy fibers and Schaffer collaterals of CA1-3 and dentate gyrus. Furthermore, P2X1 receptor is downregulated by pharmacological treatment with TNP-ATP, which is also found neuroprotective against ischemic cell death. Morphological studies conducted through immunofluorescence and confocal analysis in primary organotypic, in dissociated cultures, and in adult rat in vivo demonstrated the neuronal colocalization of P2X1 protein with neurofilament light chain and neuronal nuclei immunoreactivity in myelinated and unmyelinated fibers of both granular and pyramidal neurons. In conclusion, with this work, we proved the neuronal distribution of P2X 1 receptor in hippocampus, and we presented evidence for a potential disadvantageous role of its expression during the path of in vitro ischemia.

Original languageEnglish
Pages (from-to)70-77
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume323
Issue number1
DOIs
Publication statusPublished - Oct 2007

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Purinergic P2X1 Receptors
Hippocampus
Cell Death
Adenosine Triphosphate
Oxygen
Glucose
Pyramidal Cells
Dentate Gyrus
Fluorescent Antibody Technique
Down-Regulation
Ischemia
Pharmacology
Therapeutics

ASJC Scopus subject areas

  • Pharmacology

Cite this

P2 receptor antagonist trinitrophenyl-adenosine-triphosphate protects hippocampus from oxygen and glucose deprivation cell death. / Cavaliere, Fabio; Amadio, Susanna; Dinkel, Klaus; Reymann, Klaus G.; Volonté, Cinzia.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 323, No. 1, 10.2007, p. 70-77.

Research output: Contribution to journalArticle

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