Microglial P2Y12 Receptor Regulates Seizure-Induced Neurogenesis and Immature Neuronal Projections

• DOI: 10.1523/jneurosci.0487-19.2019
• Publication Date: 2019-10-09T21:49:18Z
• Authors: Mingshu Mo; Ukpong B. Eyo; Manling Xie; Jiyun Peng; Dale B. Bosco; Anthony D. Umpierre; Xiaoqin Zhu; Dai-Shi Tian; Pingyi Xu; Long-Jun Wu
• Keywords: Male; Mice, Inbred C57BL; Neurons; Mice; 0303 health sciences; 03 medical and health sciences; Seizures; Neurogenesis; Animals; Mice, Transgenic; Microglia; Receptors, Purinergic P2Y12

Seizures are common in humans with various etiologies ranging from congenital aberrations to acute injuries that alter the normal balance of brain excitation and inhibition. A notable consequence seizures is induction aberrant neurogenesis increased immature neuronal projections. However, regulatory mechanisms governing these features during epilepsy development not fully understood. Recent studies show microglia, brain's resident immune cell, contribute regulate seizure phenotypes. role microglia neurogenic contexts has been adequately investigated. To address this question, we coupled intracerebroventricular kainic acid model current pharmacogenetic approaches eliminate male mice. We promote seizure-induced subsequent projections above below pyramidal neurons between DG CA3 regions. Furthermore, identify microglial P2Y12 receptors (P2Y12R) as a participant process. Together, our results implicate P2Y12R signaling epileptogenesis provide further evidence for targeting general specific ameliorate proepileptogenic processes.SIGNIFICANCE STATEMENT Epileptogenesis process by which develops epilepsy. Several processes have identified confer such epileptic characteristics, including Understanding changes critical developing therapies restrain epileptogenesis. investigated purinergic selectively expressed cells. report, first time, both These indicate enhance promoting suggest axis could be novel therapeutic strategy clinic.