Effects of noradrenaline on neuronal NOS2 expression and viability
Effects of noradrenaline on neuronal NOS2 expression and viability
复制标题
DOI：
10.1089/ars.2006.8.885
复制
发表时间：
2006-05-01
影响因子：
6.6
通讯作者：
Feinstein, Douglas L.
中科院分区：
文献类型：
--
作者：
Madrigal, Jose L. M.;Dello Russo, Cinzia;Feinstein, Douglas L.
作者先前发现，来自激活的小胶质细胞的条件培养液(CM)增加了皮质神经元中诱导型一氧化氮合酶(NOS2)的表达。在这里，他们研究了去甲肾上腺素(NA)减少神经元NOS2或细胞死亡的能力。小胶质细胞与脂多糖(LPS)孵育后，用CM激活原代培养的小鼠皮质神经元。神经元NOS2通过增加亚硝酸盐蓄积、NOS2 mRNA水平和NO敏感探针DAF-2DA的荧光来评估。NOS2的诱导与神经元乳酸脱氢酶释放增加有关。当在小胶质细胞激活过程中加入NA时，神经元NOS2的表达显著减少(约70%)；相反，如果NA与CM一起加入神经元，则NOS2的表达减少较少(约35%)。添加到小胶质细胞或神经元的NA可减少神经元乳酸脱氢酶的释放。单独或用IL1受体拮抗剂阻断肿瘤坏死因子α抗体可部分减少神经细胞死亡和NOS2。NA与神经元孵育可增加IKBα，从而减少NOS2。这些结果表明，NA调节神经元NOS2的表达和损伤，这些作用主要是由于抑制了小胶质细胞释放的因子。NA的紊乱可能会增加炎症反应，从而加剧神经元损伤。
The authors previously showed that conditioned media (CM) from activated microglia increased inducible nitric oxide synthase (NOS2) in cortical neurons. Here they examined the ability of noradrenaline (NA) to reduce neuronal NOS2 or cell death. Primary mouse cortical neurons were activated using CM from microglia incubated with lipopolysaccharide (LPS). Neuronal NOS2 was assessed by increases in nitrite accumulation, and increases in NOS2 mRNA levels and fluorescence of the NO-sensitive probe DAF-2 DA. NOS2 induction was associated with an increase in neuronal LDH release. When NA was added during microglial activation, neuronal NOS2 was significantly reduced (by approximately 70%); in contrast if NA was added to the neurons along with CM, there was less reduction (about 35% decrease) in NOS2 expression. NA added to either microglia or to neurons reduced neuronal LDH release comparably. Pretreatment of CM with blocking antibody to TNF alpha, alone or with IL1-receptor antagonist, partially reduced neuronal cell death and NOS2. Incubation of neurons with NA increased IkB alpha, which could reduce NOS2. These results demonstrate that NA modulates neuronal NOS2 expression and damage, and that these effects are primarily due to inhibition of microglia released factors. Perturbations of NA could exacerbate neuronal damage by allowing for increased inflammatory responses.