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Effects of Creatine and β-guanidinopropionic Acid and Alterations in Creatine Transporter and Creatine Kinases Expression in Acute Seizure and Chronic Epilepsy Models

Overview
Journal BMC Neurosci
Publisher Biomed Central
Specialty Neurology
Date 2010 Oct 29
PMID 20979657
Citations 4
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Abstract

Background: In order to confirm the roles of creatine (Cr) in epilepsy, we investigated the anti-convulsive effects of Cr, creatine transporter (CRT) and creatine kinases (CKs) against chemical-induced acute seizure activity and chronic epileptic seizure activity.

Results: Two hr after pilocarpine (PILO)-seizure induction, ubiquitous mitochondrial CK (uMtCK) immunoreactivity was unaltered as compared to control level. However, brain-type cytoplasm CK (BCK) immunoreactivity was decreased to 70% of control level. CRT immunoreactivity was decreased to 60% of control level. Following Cr or Tat-CK treatment, uMtCK or CRT immunoreactivity was unaffected, while BCK immunoreactivity in Cr treated group was increased to 3.6-fold of control levels. β-Guanidinopropionic acid (GPA, a competitive CRT inhibitor) reduced BCK and CRT expression. In addition, Cr and tat-BCK treatment delayed the beginning of seizure activity after PILO injection. However, GPA treatment induced spontaneous seizure activity without PILO treatment. In chronic epilepsy rats, both uMtCK and CRT immunoreactivities were reduced in the hippocampus. In contrast, BCK immunoreactivity was similar to that observed in control animals. Cr-, GPA and tat-BCK treatment could not change EEG.

Conclusion: Cr/CK circuit may play an important role in sustaining or exacerbating acute seizure activity, but not chronic epileptic discharge.

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Differences in the hippocampal frequency of creatine inclusions between the acute and latent phases of pilocarpine model defined using synchrotron radiation-based FTIR microspectroscopy.

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The effect of the creatine analogue beta-guanidinopropionic acid on energy metabolism: a systematic review.

Oudman I, Clark J, Brewster L PLoS One. 2013; 8(1):e52879.

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Synchrotron radiation Fourier-transform infrared and Raman microspectroscopy study showing an increased frequency of creatine inclusions in the rat hippocampal formation following pilocarpine-induced seizures.

Dulinska J, Setkowicz Z, Janeczko K, Sandt C, Dumas P, Uram L Anal Bioanal Chem. 2011; 402(7):2267-74.

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