Huang Li, Zhao Shidi, Lu Wei, Guan Sudong, Zhu Yan, Wang Jin-Hui
Department of Pathophysiology, Bengbu Medical College, Bengbu Anhui, China 233000.
Collaborative Innovation Center for Neurodegenerative Disorders in Shandong, Qingdao University, Medical College, 38 Dengzhou, Shandong China 266021.
PLoS One. 2015 Oct 16;10(10):e0140324. doi: 10.1371/journal.pone.0140324. eCollection 2015.
Acidosis impairs cognitions and behaviors presumably by acidification-induced changes in neuronal metabolism. Cortical GABAergic neurons are vulnerable to pathological factors and their injury leads to brain dysfunction. How acidosis induces GABAergic neuron injury remains elusive. As the glia cells and neurons interact each other, we intend to examine the role of the astrocytes in acidosis-induced GABAergic neuron injury.
Experiments were done at GABAergic cells and astrocytes in mouse cortical slices. To identify astrocytic involvement in acidosis-induced impairment, we induced the acidification in single GABAergic neuron by infusing proton intracellularly or in both neurons and astrocytes by using proton extracellularly. Compared the effects of intracellular acidification and extracellular acidification on GABAergic neurons, we found that their active intrinsic properties and synaptic outputs appeared more severely impaired in extracellular acidosis than intracellular acidosis. Meanwhile, extracellular acidosis deteriorated glutamate transporter currents on the astrocytes and upregulated excitatory synaptic transmission on the GABAergic neurons. Moreover, the antagonists of glutamate NMDA-/AMPA-receptors partially reverse extracellular acidosis-induced injury in the GABAergic neurons.
Our studies suggest that acidosis leads to the dysfunction of cortical GABAergic neurons by astrocyte-mediated excitotoxicity, in addition to their metabolic changes as indicated previously.
酸中毒可能通过酸化诱导的神经元代谢变化损害认知和行为。皮质γ-氨基丁酸（GABA）能神经元易受病理因素影响，其损伤会导致脑功能障碍。酸中毒如何诱导GABA能神经元损伤仍不清楚。由于神经胶质细胞和神经元相互作用，我们打算研究星形胶质细胞在酸中毒诱导的GABA能神经元损伤中的作用。
在小鼠皮质切片中的GABA能细胞和星形胶质细胞上进行了实验。为了确定星形胶质细胞参与酸中毒诱导的损伤，我们通过细胞内注入质子在单个GABA能神经元中诱导酸化，或通过细胞外使用质子在神经元和星形胶质细胞两者中诱导酸化。比较细胞内酸化和细胞外酸化对GABA能神经元的影响，我们发现与细胞内酸中毒相比，细胞外酸中毒时其主动内在特性和突触输出受损更严重。同时，细胞外酸中毒使星形胶质细胞上的谷氨酸转运体电流恶化，并上调GABA能神经元上的兴奋性突触传递。此外，谷氨酸N-甲基-D-天冬氨酸（NMDA）/α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体拮抗剂可部分逆转细胞外酸中毒诱导的GABA能神经元损伤。
我们的研究表明，除了先前指出的代谢变化外，酸中毒还通过星形胶质细胞介导的兴奋性毒性导致皮质GABA能神经元功能障碍。
