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Effect of the calcineurin inhibitor FK506 on K+-Cl- cotransporter 2 expression in the mouse hippocampus after kainic acid-induced status epilepticus.
Shin, Hyun Joo; Jeon, Byeong Tak; Kim, Jungmee; Jeong, Eun Ae; Kim, Myeung Ju; Lee, Dong Hoon; Kim, Hyun Joon; Kang, Sang Soo; Cho, Gyeong Jae; Choi, Wan Sung; Roh, Gu Seob.
Afiliação
  • Shin HJ; Department of Anatomy and Neurobiology, Institute of Health Sciences, Medical Research Center for Neural Dysfunction, School of Medicine, Gyeongsang National University, 816 Beongil 15 Jinju-daero, Jinju, Gyeongnam 660-290, Republic of Korea.
J Neural Transm (Vienna) ; 119(6): 669-77, 2012 Jun.
Article em En | MEDLINE | ID: mdl-22160488
Calcineurin (CaN)-mediated excitotoxicity impairs γ-aminobutyric acid (GABA) transmission and induces neuronal apoptosis. Ca(2+)-dependent K(+)-Cl(-) cotransporter 2 (KCC2) participates in GABAergic inhibitory transmission. However, the mechanism by which CaN mediates GABA receptor-mediated KCC2 in seizures is not fully understood. In the present study, we investigated the altered expression of KCC2 and the effects of the CaN inhibitor FK506 on KCC2 expression in the mouse hippocampus following kainic acid (KA) treatment. FK506 was injected twice 24 h and 30 min before KA treatment and then mice were treated with KA and killed 2 days later. FK506 had anticonvulsant effect on KA-induced seizure activities. CaN cleavage was evident in the hippocampus 24 h after KA treatment. FK506 pretreatment blocked the truncation of CaN in the KA-treated hippocampus. Cresyl violet and TUNEL staining showed that FK506 prevented KA-induced hippocampal cell death. In particular, Western blot analysis showed that KCC2 expression was time dependent, with a peak at 6 h and a return to decreased levels at 48 h, whereas FK506 pretreatment inhibited the KA-induced decrease in KCC2 expression in the hippocampus. Immunofluorescence showed that FK506 pretreatment protected the loss of inhibitory GABAergic KCC2-expressing neurons following KA treatment. Taken together, these results provide evidence that altered KCC2 expression may be associated with Ca(2+)-mediated seizure activity and indicate that neuron-specific KCC2 may be involved in neuroprotection after seizures.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Estado Epiléptico / Tacrolimo / Simportadores / Inibidores de Calcineurina / Hipocampo / Imunossupressores Limite: Animals Idioma: En Revista: J Neural Transm (Vienna) Ano de publicação: 2012 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Estado Epiléptico / Tacrolimo / Simportadores / Inibidores de Calcineurina / Hipocampo / Imunossupressores Limite: Animals Idioma: En Revista: J Neural Transm (Vienna) Ano de publicação: 2012 Tipo de documento: Article