title: Acidosis-Induced Dysfunction of Cortical GABAergic Neurons through Astrocyte-Related Excitotoxicity.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathophysiology, Bengbu Medical College, Bengbu Anhui, China 233000.
authors.forename: Li
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Pathophysiology, Bengbu Medical College, Bengbu Anhui, China 233000.
authors.forename: Shidi
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Collaborative Innovation Center for Neurodegenerative Disorders in Shandong, Qingdao University, Medical College, 38 Dengzhou, Shandong China 266021.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Pathophysiology, Bengbu Medical College, Bengbu Anhui, China 233000.
authors.forename: Sudong
authors.initials: S
authors.lastname: Guan
authors.affiliation: Department of Pathophysiology, Bengbu Medical College, Bengbu Anhui, China 233000.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Institute of Biophysics, Chinese Academy of Sciences, Beijing China 100101.
authors.forename: Jin-Hui
authors.initials: JH
authors.lastname: Wang
mesh_terms: D000138:Acidosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001928:Brain Diseases, Metabolic / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D059330:GABAergic Neurons / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
chemical_list: D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate