Status epilepticus alters hippocampal PKAβ and PKAγ expression in mice☆
Received 9 September 2009; received in revised form 12 June 2010; accepted 17 June 2010. published online 15 July 2010.
Abstract
Objectives
To investigate the localization and progressive changes of cyclic-AMP dependent protein kinase (cPKA) in the mouse hippocampus at acute stages during and after pilocarpine induced status epilepticus.
Methods
Pilocarpine induced status epilepticus mice were sacrificed 30min, 2h or 1 day after the start of a ∼7h lasting status as assessed by video-electroencephalography. Brains were processed for quantitative immunohistochemistry of hippocampal cPKAβ and cPKAγ, and immunohistochemical co-localization of cPKAβ and cPKAγ with calbindin (CB), calretinin (CR), and parvalbumin (PV).
Results
Based on anatomical and morphological assessment, cPKAβ was primarily expressed by principal cells and cPKAγ by interneurons. In CA1, cPKAβ co-localized with 76% of CB, 41% of CR, and 95% of PV-immunopositive cells, while cPKAγ co-localized with 50% of CB, 29% of CR, and 80% of PV-immunopositive cells. Upon induction of status epilepticus, cPKAβ expression was transiently reduced in CA1, whereas cPKAγ expression was sustainably reduced.
Conclusion
cPKA may play an important role in neuronal hyperexcitability, death and epileptogenesis during and after pilocarpine induced status epilepticus.
aInstitute of Neurobiology, School of Medicine, Xi’an Jiaotong University, Xi’an, PR China
bTemasek Laboratories, National University of Singapore, Singapore
cDepartment of Anatomy, National University of Singapore, Singapore
Corresponding author at: Temasek Laboratories, National University of Singapore, 5A Engineering Drive 1, #06-27, Singapore 117411, Singapore. Tel.: +65 66011094; fax: +65 68726840.
☆ Supported by research grant (No: NMRC/0960/2005) from the National Medical Research Council (NMRC) of Singapore as trainee in Epilepsy Research Lab. This study was supported by NMRC grants (No: NMRC/0960/2005) and Singhealth Research Foundation (Nos: SHF/FG217P/2005 and SHF/FG382P/2007) to FR Tang and Guang Hua medical research grant (0203411) from Xi’an Jiaotong University.
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