Microglia are the main form of immune defense in the central nervous system. Microglia express phosphatidylinositol 3-kinase (PI3K), which has been shown to play a significant role in synaptic plasticity in neurons and inflammation via microglia. This study shows that microglial PI3K is regulated epigenetically through histone modifications and posttranslationally through sumoylation and is involved in long-term potentiation (LTP) by modulating the expression of brain-derived neurotrophic factor (BDNF), which has been shown to be involved in neuronal synaptic plasticity. Sodium butyrate, a histone deacetylase inhibitor, upregulates PI3K expression, the phosphorylation of its downstream effectors, AKT and cAMP response element-binding protein (CREB), and the expression of BDNF in microglia, suggesting that BDNF secretion is regulated in microglia via epigenetic regulation of PI3K. Further, knockdown of SUMO1 in BV2 microglia results in a decrease in the expression of PI3K, the phosphorylation of AKT and CREB, as well as the expression of BDNF. These results suggest that microglial PI3K is epigenetically regulated by histone modifications and posttranslationally modified by sumoylation, leading to altered expression of BDNF. Whole-cell voltage-clamp showed the involvement of microglia in neuronal LTP, as selective ablation or disruption of microglia with clodronate in rat hippocampal slices abolished LTP. However, LTP was rescued when the same hippocampal slices were treated with active PI3K or BDNF, indicating that microglial PI3K/AKT signaling contributes to LTP and synaptic plasticity. Understanding the mechanisms by which microglial PI3K influences synapses provides insights into the ways it can modulate synaptic transmission and plasticity in learning and memory.

中文翻译：

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大鼠小胶质磷脂酰肌醇3-激酶途径的表观遗传学调控，其参与了长期的增强作用和突触可塑性。

小胶质细胞是中枢神经系统免疫防御的主要形式。小胶质细胞表达磷脂酰肌醇3-激酶（PI3K），已显示在小胶质细胞中神经元的突触可塑性和炎症中起重要作用。这项研究表明，小胶质细胞PI3K通过组蛋白修饰在表观遗传上受到调控，并通过sumoylation在翻译后进行调控，并通过调节脑源性神经营养因子（BDNF）的表达而参与长期增强（LTP），该过程已被证明与神经元有关。突触可塑性。组蛋白脱乙酰基酶抑制剂丁酸钠上调PI3K表达，其下游效应子的磷酸化，AKT和cAMP反应元件结合蛋白（CREB）以及小胶质细胞中BDNF的表达，提示BDNF的分泌通过PI3K的表观遗传调控而在小胶质细胞中得到调控。此外，BMO2小胶质细胞中SUMO1的敲低导致PI3K表达，AKT和CREB的磷酸化以及BDNF的表达降低。这些结果表明，小胶质细胞PI3K受组蛋白修饰表观遗传调控，而被SUMO化修饰后翻译后修饰，导致BDNF表达改变。全细胞电压钳显示小胶质细胞参与神经元LTP，因为大鼠海马切片中的氯膦酸盐对小胶质细胞的选择性消融或破坏消除了LTP。但是，当用活性PI3K或BDNF处理相同的海马切片时，LTP得以挽救，表明小胶质PI3K / AKT信号传导有助于LTP和突触可塑性。