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Acidosis-Induced Dysfunction of Cortical GABAergic Neurons through Astrocyte-Related Excitotoxicity.

Huang L, Zhao S, Lu W, Guan S, Zhu Y, Wang JH - PLoS ONE (2015)

Bottom Line: Acidosis impairs cognitions and behaviors presumably by acidification-induced changes in neuronal metabolism.Meanwhile, extracellular acidosis deteriorated glutamate transporter currents on the astrocytes and upregulated excitatory synaptic transmission on 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathophysiology, Bengbu Medical College, Bengbu Anhui, China 233000.

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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus

Extracellular acidosis impairs the active intrinsic properties of the cortical GABAergic neurons dominantly.A) shows the differences of spike frequencies between control and intracellular acidosis (red bar) as well as between control and extracellular acidosis (blue bar; asterisk, p<0.05; one-way ANOVA). B) shows the differences of spike refractory periods between control and intracellular acidosis (red bar) as well as between control and extracellular acidosis (blue bar; one asterisk, p<0.05; one-way ANOVA). C) shows the differences of spike threshold potentials between control and intracellular acidosis (red bar) as well as between control and extracellular acidosis (blue bar; one asterisk, p<0.05; one-way ANOVA).
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pone.0140324.g004: Extracellular acidosis impairs the active intrinsic properties of the cortical GABAergic neurons dominantly.A) shows the differences of spike frequencies between control and intracellular acidosis (red bar) as well as between control and extracellular acidosis (blue bar; asterisk, p<0.05; one-way ANOVA). B) shows the differences of spike refractory periods between control and intracellular acidosis (red bar) as well as between control and extracellular acidosis (blue bar; one asterisk, p<0.05; one-way ANOVA). C) shows the differences of spike threshold potentials between control and intracellular acidosis (red bar) as well as between control and extracellular acidosis (blue bar; one asterisk, p<0.05; one-way ANOVA).

Mentions: In addition, the influences of extracellular acidosis on spiking abilities and intrinsic properties at GABAergic neurons are significantly severer than the influences of intracellular acidosis (Fig 4A–4C). Therefore, the impairment of GABAergic neurons in their excitability and synaptic outputs is more severe in extracellular acidosis than intracellular acidosis. In terms of the mechanisms underlying these facts, we hypothesized that extracellular acidosis may influence the nerve cells around GABAergic neurons, such as the astrocytes and the glutamatergic neurons, to indirectly make additional impairment to GABAergic neurons, besides the effect of intracellular protons on GABAergic neurons. This hypothesis was based on the reports that the astrocytes were involved in neuronal injury [29,30] and the impairment of GABAergic neurons was induced by neuronal excitotoxicity [22,31,32].


Acidosis-Induced Dysfunction of Cortical GABAergic Neurons through Astrocyte-Related Excitotoxicity.

Huang L, Zhao S, Lu W, Guan S, Zhu Y, Wang JH - PLoS ONE (2015)

Extracellular acidosis impairs the active intrinsic properties of the cortical GABAergic neurons dominantly.A) shows the differences of spike frequencies between control and intracellular acidosis (red bar) as well as between control and extracellular acidosis (blue bar; asterisk, p<0.05; one-way ANOVA). B) shows the differences of spike refractory periods between control and intracellular acidosis (red bar) as well as between control and extracellular acidosis (blue bar; one asterisk, p<0.05; one-way ANOVA). C) shows the differences of spike threshold potentials between control and intracellular acidosis (red bar) as well as between control and extracellular acidosis (blue bar; one asterisk, p<0.05; one-way ANOVA).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608795&req=5

pone.0140324.g004: Extracellular acidosis impairs the active intrinsic properties of the cortical GABAergic neurons dominantly.A) shows the differences of spike frequencies between control and intracellular acidosis (red bar) as well as between control and extracellular acidosis (blue bar; asterisk, p<0.05; one-way ANOVA). B) shows the differences of spike refractory periods between control and intracellular acidosis (red bar) as well as between control and extracellular acidosis (blue bar; one asterisk, p<0.05; one-way ANOVA). C) shows the differences of spike threshold potentials between control and intracellular acidosis (red bar) as well as between control and extracellular acidosis (blue bar; one asterisk, p<0.05; one-way ANOVA).
Mentions: In addition, the influences of extracellular acidosis on spiking abilities and intrinsic properties at GABAergic neurons are significantly severer than the influences of intracellular acidosis (Fig 4A–4C). Therefore, the impairment of GABAergic neurons in their excitability and synaptic outputs is more severe in extracellular acidosis than intracellular acidosis. In terms of the mechanisms underlying these facts, we hypothesized that extracellular acidosis may influence the nerve cells around GABAergic neurons, such as the astrocytes and the glutamatergic neurons, to indirectly make additional impairment to GABAergic neurons, besides the effect of intracellular protons on GABAergic neurons. This hypothesis was based on the reports that the astrocytes were involved in neuronal injury [29,30] and the impairment of GABAergic neurons was induced by neuronal excitotoxicity [22,31,32].

Bottom Line: Acidosis impairs cognitions and behaviors presumably by acidification-induced changes in neuronal metabolism.Meanwhile, extracellular acidosis deteriorated glutamate transporter currents on the astrocytes and upregulated excitatory synaptic transmission on 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathophysiology, Bengbu Medical College, Bengbu Anhui, China 233000.

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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus