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NEUROPHARMACOLOGY

P2 Receptor Antagonist Trinitrophenyl-Adenosine-Triphosphate Protects Hippocampus from Oxygen and Glucose Deprivation Cell Death

Santa Lucia Foundation, Rome, Italy (F.C., S.A., C.V.); INBIOMED Foundation, San Sebastian, Spain (F.C.); Leibniz Institute for Neurobiology, Magdeburg, Germany (K.D., K.G.R.); Research Institute for Applied Neuroscience, FAN GmbH, Magdeburg, Germany (K.G.R.); and Consiglio Nazionale delle Ricerche, Institute of Neurobiology and Molecular Medicine, Rome, Italy (C.V.)

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 down-regulated 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 P2X₁ receptor in hippocampus, and we presented evidence for a potential disadvantageous role of its expression during the path of in vitro ischemia.

Address correspondence to: Dr. Fabio Cavaliere, Santa Lucia Foundation, Via del Fosso di Fiorano, 64, I-00143 Rome, Italy. E-mail: f.cavaliere{at}hsantalucia.it