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Role for Pro-inflammatory Cytokines in Regulating Expression of GABA Transporter Type 1 and 3 in Specific Brain Regions of Kainic Acid-Induced Status Epilepticus

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Abstract

In general, pro-inflammatory cytokines (PICs) contribute to regulation of epilepsy-associated pathophysiological processes in the central nerve system. In this report, we examined the specific activation of PICs, namely IL-1β, IL-6 and TNF-α in rat brain after kainic acid (KA)-induced status epilepticus (SE). Also, we examined the role played by PICs in regulating expression of GABA transporter type 1 and 3 (GAT-1 and GAT-3, respectively), which are the two important subtypes of GATs responsible for the regulation of extracellular GABA levels in the brain. Our results show that IL-1β, IL-6 and TNF-α were significantly increased in the parietal cortex, hippocampus and amygdala of KA-rats as compared with sham control animals (P < 0.05, KA rats vs. control rats). KA-induced SE also significantly increased (P < 0.05 vs. controls) the protein expression of GAT-1 and GAT-3 in those brain regions. In addition, central administration of antagonists to IL-1β and TNF-α receptors significantly attenuated amplified GAT-1 and GAT-3 (P < 0.05 vs. vehicle control for each antagonist group). However, antagonist to IL-6 receptor failed to attenuate enhancement in expression of GAT-1 and GAT-3 induced by KA-induced SE. Overall, our data demonstrate that PIC pathways are activated in the specific brain regions during SE which thereby selectively leads to upregulation of GABA transporters. As a result, it is likely that de-inhibition of GABA system is increased in the brain. This support a role for PICs in engagement of the adaptive mechanisms associated with epileptic activity, and has pharmacological implications to target specific PICs for neuronal dysfunction and vulnerability related to epilepsy.

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Authors and Affiliations

  1. Department of Neurosurgery and Epilepsy Center, The Second Affiliated Hospital of Dalian Medical University, 467 Zhong Shan Road, Dalian, 116011, Liaoning, China

    Jing Su, Jian Yin, Wei Qin, Suxu Sha & Jun Xu

  2. Department of Neurology, The First Affiliated Hospital of Dalian Medical University, 222 Zhong Shan Road, Dalian, 116000, Liaoning, China

    Changbin Jiang

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  1. Jing Su
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  2. Jian Yin
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  3. Wei Qin
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  4. Suxu Sha
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  5. Jun Xu
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  6. Changbin Jiang
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Correspondence to Jian Yin or Changbin Jiang.

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Su, J., Yin, J., Qin, W. et al. Role for Pro-inflammatory Cytokines in Regulating Expression of GABA Transporter Type 1 and 3 in Specific Brain Regions of Kainic Acid-Induced Status Epilepticus. Neurochem Res 40, 621–627 (2015). https://doi.org/10.1007/s11064-014-1504-y

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  • DOI: https://doi.org/10.1007/s11064-014-1504-y

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