ATP-sensitive purine receptors regulate the function of neural progenitor cells in the brain

Purine receptors may be classified to the P1 und P2 types, responding to extracellular adenosine and ATP/ADP, respectively. P2receptors consist of two subtypes termed P2X (ligand-gated cationic channels) and P2Y (G protein-coupled receptors). Adultneural progenitor cells (NPCs) are located at the so called neurogenic niches of the subventricular zone below the wall of thelateral ventricle and the subgranular zone of the hippocampal dentate gyrus. These NPCs pass through transient developmentalstates, and eventually give rise to neurons, which become integrated into existing neuronal circuits of the olphactory bulb andhippocampus. Whereas in case of neurodegenerative diseases newly formed NPCs replace e.g. damaged hippocampal neuronsand are thereby beneficial, pathological seizure activity may have deleterious consequences. Status epilepticus causes theexcessive proliferation NPCs, their migration to ectopic loci e.g. in the hilus hippocampi and consequently the chronicmanifestation of a one-time epileptic fit. It is noteworthy that any type of damage afflicted onto neurons including metaboliclimitation during epilepsy may release large quantities of ATP from neurons, glial cells and endothelium. The subsequentlystimulated P2Y1 receptors will facilitate proliferation, migration and differentiation of NPCs, while P2X7 receptors will causenecrosis and apoptosis. Thus, the same ATP/ADP molecule might cause opposing effects, albeit at a different time scale, by bothincreasing the number of NPCs via P2Y1 receptor activation and decreasing this number by P2X7 receptor stimulation. Wesuggest that P2Y1 receptors after a status epilepticus may increase the ATP-induced proliferation/ectopic migration of NPCs; theP2X7 receptor mediated necrosis/apoptosis might counteract these effects, which would otherwise lead to a chronic manifestationof recurrent epileptic fits.

کلیدواژه ها:

Purine receptors ، Status epilepticus ، Hippocampal dentate gyrus