Evidence against enhanced glutamate transport in the anticonvulsant mechanism of the ketogenic diet.
Excessive glutamatergic neurotransmission is considered an underlying factor of epilepsy. Energy-dependent glutamate transporters clear extracellular glutamate to limit neuronal excitability. Evidence suggests that reduced expression and/or activity of glutamate transporters contribute to hyperexcitability and progressive seizure activity in rats. By comparison, treatment with the anticonvulsant ketogenic diet (KD) results in increased mRNA expression of the neuronal glutamate transporter EAAC1, elevated energy reserves, and an increased resistance to seizures in rats. The goal of the current study was to determine whether the expression and/or re-uptake activity of glutamate transporters were elevated in hippocampal tissue of rats after KD treatment. Rats were fed either a ketogenic- or control diet for 4-5 weeks. Western blot analysis showed that protein levels of EAAC1, GLT-1 and GLAST glutamate transporters were not changed in hippocampus, cerebral cortex, or cerebellum after KD. Electron microscopic evidence indicated that the KD did not affect hippocampal EAAC1 distribution. In addition, the re-uptake activity of (3)H-glutamate into hippocampal proteoliposomes was similar in both KD and control tissue extracts. These multiple studies suggest that the anticonvulsant nature of the KD does not stem from enhanced glutamate re-uptake.
Bough
Kristopher J
KJ
Department of Pharmacology, Emory University, Atlanta, GA, USA. kbough96@yahoo.com <kbough96@yahoo.com>
Paquet
Maryse
M
Paré
Jean-François
JF
Hassel
Bjørnar
B
Smith
Yoland
Y
Hall
Randy A
RA
Dingledine
Raymond
R
D027322:Amino Acid Transport System X-AG / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D004827:Epilepsy / Q000178:diet therapy* / Q000378:metabolism*; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D050580:Excitatory Amino Acid Transporter 3 / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007659:Ketones / Q000097:blood / Q000378:metabolism*; D008297:Male; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013347:Subcellular Fractions / Q000378:metabolism
D027322:Amino Acid Transport System X-AG; D027342:Excitatory Amino Acid Transporter 2; D050580:Excitatory Amino Acid Transporter 3; D007659:Ketones; D009419:Nerve Tissue Proteins; C493398:Slc1a1 protein, rat; D018698:Glutamic Acid