PT - JOURNAL ARTICLE AU - Mingshu Mo AU - Ukpong B. Eyo AU - Manling Xie AU - Jiyun Peng AU - Dale B. Bosco AU - Anthony D. Umpierre AU - Xiaoqin Zhu AU - Dai-Shi Tian AU - Pingyi Xu AU - Long-Jun Wu TI - Microglial P2Y12 receptors regulate seizure-induced neurogenesis and immature neuronal projections AID - 10.1523/JNEUROSCI.0487-19.2019 DP - 2019 Oct 09 TA - The Journal of Neuroscience PG - 0487-19 4099 - http://www.jneurosci.org/content/early/2019/10/08/JNEUROSCI.0487-19.2019.short 4100 - http://www.jneurosci.org/content/early/2019/10/08/JNEUROSCI.0487-19.2019.full AB - 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 of seizures is the induction of aberrant neurogenesis and increased immature neuronal projections. However, regulatory mechanisms governing these features during epilepsy development are not fully understood. Recent studies show that microglia, the brain's resident immune cell, contribute to normal neurogenesis and regulate seizure phenotypes. However, the role of microglia in aberrant neurogenic seizure contexts has not been adequately investigated. To address this question, we coupled the intracerebroventricular kainic acid (KA) model with current pharmacogenetic approaches to eliminate microglia in male mice. We show that microglia promote seizure-induced neurogenesis and subsequent seizure-induced immature neuronal projections above and below the pyramidal neurons between the DG and the CA3 regions. Furthermore, we identify microglial P2Y12 receptors (P2Y12R) as a participant in this neurogenic process. Together, our results implicate microglial P2Y12R signaling in epileptogenesis and provide further evidence for targeting microglia in general and microglial P2Y12R in specific to ameliorate pro-epileptogenic processes.Signifiance StatementEpileptogenesis is a process by which the brain develops epilepsy. Several processes have been identified that confer the brain with such epileptic characteristics, including aberrant neurogenesis and increased immarture neuronal projections. Understanding the mechanisms that promote such changes is critical in developing therapies to adequately restrain epileptogenesis. We investigated the role of purinergic P2Y12 receptors selectively expressed by microglia, the resident brain immune cells. We report for the first time that microglia in general and microglial P2Y12 receptors in specific promote both aberrant neurogenesis and increased immature neuronal projections. These results indicate that microglia enhance epileptogenesis by promoting these processes and suggest that targeting this immune axis could be a novel therapeutic strategy in the clinic.