Fig 1.
Epileptiform discharges induced by Mg2+-free artificial cerebral spinal fluid (ACSF).
(A) Field-potential recording from the CA1 region of acute hippocampal slices showing regular spontaneous activity induced by Mg2+ free ACSF. Application of 10μM rosiglitazone significantly decreased firing frequency of epileptiform discharges. Pretreatement with 2μM or 20μM GW9662 did not block the anti-convulsive effect of 10μM rosiglitazone. (B) Quantification of spike frequency before and after application of 1μM and 10μM rosiglitazone showing that10μM rosiglitazone can significantly suppresses spike frequency. Application of 2μM or 20μM GW9662 didn’t block the attenuation of spike frequency from 10μM rosiglitazone. (C) Quantification of spike amplitude during control ACSF, GW9662, and rosiglitazone infusion. Application of 1μM and 10μM can suppress spike amplitude. The decrease in spike amplitude was reversed by pretreatment with 20μM GW9662. *P <0.05 **P<0.01.
Fig 2.
Effects of rosiglitazone on CA1-Schaffer collateral field evoked potentials (fEPSPs) and CA1 pyramidal cell miniature excitatory postsynaptic currents (mEPSC).
(A) Representative traces of fEPSPs before (black color) and after application of 1,5,10μM rosiglitazone with/without 20μM GW9662 treatment for 30 minutes (red color). (B) The slope of first fEPSPs were suppressed significantly by 5 and 10μM rosiglitazone. (C) Cotreatment with 20μM GW9662 partially reversed the suppression of fEPSP slope induced by 10μM rosiglitazone. (D) Quantification of fEPSP slope after rosiglitazone/GW9662 treatment for 30 minutes. (E) Application of 10μM rosilglitazone significantly increased pair-pulse ratio on CA1-Schaffer collateral fEPSPs, which indicates rosiglitazone significantly suppresses presynaptic neurotransmitter release. This effect can be completely reverse by pretreatment with 20μM GW9662. (F) Miniature EPSCs recorded on CA1 pyrimidal cells. Application of 10μM rosiglitazone significantly suppressed mEPSC frequency but not amplitude. Cumulative probability of mEPSC inter-event interval (P<0.001 by Kolmogorov–Smirnov test) and mEPSC amplitude (P = 0.18 by K-S test) from the representative trace of mEPSC were illustrated. *P<0.05 **P<0.01.
Fig 3.
Rosiglitazone protected cultured hippocampal slices from (n-Methyl-D-Aspartate) NMDA-induced excitotoxicity.
(A) Representative images of fluorescence intensity after NMDA treatment with/without rosiglitazone rescue. Bright: bright-field microscopy, Fluore: fluorescence microscopy (B) Quantitative results for fluorescence intensity after NMDA treatment with/without rosiglitazone rescue. The PI fluorescence intensity was normalized by those slices treated in control medium. Application of 40μM NMDA significantly increased PI density in dentate gyrus, CA3 and CA1 areas of hippocampus. Application of 10μM rosiglitazone significantly suppressed neuronal damage by NMDA in the dentate gyrus, CA3 and CA1 areas of the hippocampus. Pretreatment with 20μM GW9662 partially reverse the neuroprotective effect of 10μM rosiglitazone in CA1 neurons. **P <0.01 compared with PI intensity of NMDA treated slices.