Department of Neuroinflammation, University College London Institute of Neurology, London, UK.
J Neurochem. 2012 Apr;121(2):287-301. doi: 10.1111/j.1471-4159.2012.07659.x. Epub 2012 Mar 13.
Microglia express three isoforms of the NADPH oxidase, Nox1, Nox2 and Nox4, with the potential to produce superoxide (O(2) ˙(-) ). Microglia also express neurotransmitter receptors, which can modulate microglial responses. In this study, microglial activity of Nox1, Nox2 and Nox4 in primary rat cultured microglia or the rodent BV2 cell line were altered by microglial neurotransmitter receptor modulation. Glutamate, GABA or ATP triggered microglial O(2) ˙(-) production via Nox activation. Nox activation was elicited by agonists of metabotropic mGlu3 receptors and by group III receptors, by GABA(A) but not GABA(B) receptors, and by purinergic P2X(7) or P2Y(2/4) receptors but not P2Y(1) receptors, and inhibited by metabotropic glutamate receptor 5 antagonists. The neurotransmitters also modulated Nox mRNA expression and NADPH activity. The activation of Nox by BzATP or GABA promoted a neuroprotective phenotype whilst the activation of Nox by glutamate promoted a neurotoxic phenotype. Taken together, these data indicate that microglial neurotransmitter receptors can signal via Nox to promote neuroprotection or neurotoxicity. This has implications for the subsequent neurotoxic profile of microglia when neurotransmitter levels may become skewed in neurodegeneration.
小胶质细胞表达三种 NADPH 氧化酶同工型，即 Nox1、Nox2 和 Nox4，它们具有产生超氧化物 (O(2)˙(-)) 的潜力。小胶质细胞还表达神经递质受体，这些受体可以调节小胶质细胞的反应。在这项研究中，通过小胶质细胞神经递质受体调节，改变了原代大鼠培养的小胶质细胞或啮齿动物 BV2 细胞系中小胶质细胞中 Nox1、Nox2 和 Nox4 的活性。谷氨酸、GABA 或 ATP 通过 Nox 激活引发小胶质细胞 O(2)˙(-)的产生。Nox 的激活是由代谢型 mGlu3 受体激动剂和 III 组受体激动剂、GABA(A)受体但不是 GABA(B)受体、嘌呤能 P2X(7)或 P2Y(2/4)受体但不是 P2Y(1)受体引起的，并被代谢型谷氨酸受体 5 拮抗剂抑制。这些神经递质还调节 Nox mRNA 表达和 NADPH 活性。BzATP 或 GABA 激活 Nox 促进了神经保护表型，而谷氨酸激活 Nox 促进了神经毒性表型。总之，这些数据表明，小胶质细胞神经递质受体可以通过 Nox 信号传递来促进神经保护或神经毒性。这对于神经递质水平在神经退行性变中可能发生倾斜时小胶质细胞随后的神经毒性特征具有重要意义。
