Purinergic P2Y12 Receptors Are Involved In Cellular Mechanisms That Regulate Susceptibility To Epilepsy And Learning And Memory

The P2Y12 receptor is a metabolic Gi protein-coupled receptor in the purinergic receptor family.Studies have shown that systemic knockout of P2Y12 receptors increased epilepsy susceptibility in mice.The P2Y12 receptors are highly expressed in microglia.However,the susceptibility to epilepsy does not increase in mice with microglial P2Y12 absence,suggesting functional expression of P2Y12 receptors on other cells.Studies have shown that the P2Y12 receptor is also expressed on oligodendrocytes（OLs）.It is generally believed that OLs play a role in the formation of myelin for neuronal axons and provide nutrition for neurons.But what role can oligodendrocytes play through the P2Y12 receptor?There is no report yet.By crossing of P2Y12^flox/flox and Plp^{Cre ER/+}transgenic mice to generate a conditional knockout（c KO）of P2Y12 mice on oligodendrocytes,this study intend to investigate the possible role of P2Y12 receptor on oligodendrocytes.Using intraperitoneal injection of the KA model,we found that the OLs P2Y12c KO mice were sensitive to KA-induced status epilepticus and had a high mortality rate.Using Morris water maze and rota-rod motor-learning model,we found that the OLs P2Y12 c KO did not affect the abilities of both spatial and motor learning memory.Using immunohistochemistry techniques,we found that the number of OL-line cells in the prefrontal cortex and hippocampus of P2Y12 KO mice decreased,which may be caused by reduced precursor cells and their differentiation ability.The present results indicate that oligodendrocytes may be involved in regulating the excitability of neuron through P2Y12 receptors,thus affecting learning,memory and epilepsy susceptibility.This study provides a scientific basis for further research on the role of oligodendrocytes in epilepsy and the direct collaborative relationship between P2Y12 receptors and OL,which opens up new ideas for further research on epilepsy and the development of new drugs.