The involvement of P2X1 receptor in pyramidal cell degeneration in the rat hippocampus after trimethyltin administration

The P2 family of receptors for adenosine 5′-triphosphate (ATP) is involved in several neuronal and glial cell functions in the central nervous system (CNS), and impaired function of these receptors is associated with both neuronal and glial dysfunction. Using quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and immunohistochemical analysis, we examined the expression profiles of P2 subtype receptors in the rat hippocampus following treatment with the neurotoxicant trimethyltin (TMT). Among the subtypes, P2X1 exhibited a unique profile, with an increase in expression prior to the onset of cell death after TMT administration, and a gradual decrease thereafter in neuronal cells in the rat hippocampus. This expression pattern was similar to that of cyclooxygenase-2 (COX-2) following TMT administration. The P2X1 antagonist NF499 strongly prevented neuronal cell death induced by TMT in the CA1 region, and successfully suppressed locomotor hyperreactivity. Furthermore, NF449 administration also inhibited COX-2 expression in the CA1 region on day 3 following TMT treatment, whereas no change was observed in the CA3. These findings suggest that P2X1 plays a primary role in TMT-induced neuronal cell death in the CA1 region.

► TMT induces selective loss of pyramidal cells in the CA3 and CA1 regions.
► Among P2 receptor subtypes, P2X1 exhibited a unique profile after TMT administration.
► P2X1 plays a primary role in TMT-induced neuronal cell death in the CA1 region.