title: 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.
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.
authors.affiliation: Department of Neurosurgery and Epilepsy Center, The Second Affiliated Hospital of Dalian Medical University, 467 Zhong Shan Road, Dalian, 116011, Liaoning, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Su
authors.forename: Jian
authors.initials: J
authors.lastname: Yin
authors.forename: Wei
authors.initials: W
authors.lastname: Qin
authors.forename: Suxu
authors.initials: S
authors.lastname: Sha
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.forename: Changbin
authors.initials: C
authors.lastname: Jiang
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D016207:Cytokines / Q000502:physiology*; D050485:GABA Plasma Membrane Transport Proteins / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D018836:Inflammation Mediators / Q000502:physiology; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D010296:Parietal Lobe / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism*
chemical_list: D016207:Cytokines; D050485:GABA Plasma Membrane Transport Proteins; D018836:Inflammation Mediators; C493415:Slc6a1 protein, rat; D007608:Kainic Acid