Effects of creatine and β-guanidinopropionic acid and alterations in creatine transporter and creatine kinases expression in acute seizure and chronic epilepsy models.
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.


CONCLUSIONS
Cr/CK circuit may play an important role in sustaining or exacerbating acute seizure activity, but not chronic epileptic discharge.
Kim
Dae Won
DW
Department of Biomedical Sciences, College of Life Science, Hallym University, Chunchon Kangwon-Do 200-702, Republic of Korea.
Yeo
Seong-Il
SI
Ryu
Hea Jin
HJ
Kim
Ji-Eun
JE
Song
Hong-Ki
HK
Kwon
Oh-Shin
OS
Choi
Soo Young
SY
Kang
Tae-Cheon
TC
D000208:Acute Disease; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002908:Chronic Disease; D003401:Creatine / Q000502:physiology*; D003402:Creatine Kinase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D004195:Disease Models, Animal; D004827:Epilepsy / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*; D006146:Guanidines / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D026901:Membrane Transport Proteins / Q000096:biosynthesis / Q000378:metabolism*; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D006146:Guanidines; D026901:Membrane Transport Proteins; D011422:Propionates; C080679:creatine transporter; D003402:Creatine Kinase; D003401:Creatine; C005775:guanidinopropionic acid