az10606120 and Status-Epilepticus

Patch-clamp recordings indicated the presence of P2X7 receptors at neural progenitor cells (NPCs) in the subgranular zone of the dentate gyrus in hippocampal brain slices prepared from transgenic nestin reporter mice. The activation of these receptors caused inward current near the resting membrane potential of the NPCs, while P2Y1 receptor activation initiated outward current near the reversal potential of the P2X7 receptor current. Both receptors were identified by biophysical/pharmacological methods. When the brain slices were prepared from mice which underwent a pilocarpine-induced status epilepticus or when brain slices were incubated in pilocarpine-containing external medium, the sensitivity of P2X7 and P2Y1 receptors was invariably increased. Confocal microscopy confirmed the localization of P2X7 and P2Y1 receptor-immunopositivity at nestin-positive NPCs. A one-time status epilepticus in rats caused after a latency of about 5 days recurrent epileptic fits. The blockade of central P2X7 receptors increased the number of seizures and their severity. It is hypothesized that P2Y1 receptors after a status epilepticus may increase the ATP-induced proliferation/ectopic migration of NPCs; the P2X7 receptor-mediated necrosis/apoptosis might counteract these effects, which would otherwise lead to a chronic manifestation of recurrent epileptic fits.

Topics: Adamantane; Adenosine Triphosphate; Aminoquinolines; Animals; Disease Models, Animal; Excitatory Amino Acid Agents; Female; Gene Expression Regulation; Green Fluorescent Proteins; Hippocampus; Male; Membrane Potentials; Mice; Mice, Transgenic; Muscarinic Agonists; Neural Stem Cells; Nucleotides; Pilocarpine; Purinergic P2X Receptor Antagonists; Receptors, Purinergic P2X7; Receptors, Purinergic P2Y1; Status Epilepticus