Decreased astroglial monocarboxylate transporter 4 expression in temporal lobe epilepsy.
Efflux of monocaroxylates like lactate, pyruvate, and ketone bodies from astrocytes through monocarboxylate transporter 4 (MCT4) supplies the local neuron population with metabolic intermediates to meet energy requirements under conditions of increased demand. Disruption of this astroglial-neuron metabolic coupling pathway may contribute to epileptogenesis. We measured MCT4 expression in temporal lobe epileptic foci excised from patients with intractable epilepsy and in rats injected with pilocarpine, an animal model of temporal lobe epilepsy (TLE). Cortical MCT4 expression levels were significantly lower in TLE patients compared with controls, due at least partially to MCT4 promoter methylation. Expression of MCT4 also decreased progressively in pilocarpine-treated rats from 12 h to 14 days post-administration. Underexpression of MCT4 in cultured astrocytes induced by a short hairpin RNA promoted apoptosis. Knockdown of astrocyte MCT4 also suppressed excitatory amino acid transporter 1 (EAAT1) expression. Reduced MCT4 and EAAT1 expression by astrocytes may lead to neuronal hyperexcitability and epileptogenesis in the temporal lobe by reducing the supply of metabolic intermediates and by allowing accumulation of extracellular glutamate.
Department of Neurosurgery and Institute for Functional Brain Disorders, Tangdu Hospital, The Fourth Military Medical University, Xi'an, People's Republic of China.
Bei
B
Liu
Le
L
Niu
Ming-Zhi
MZ
Shen
Lei
L
Gao
Chao
C
Wang
Jie
J
Li
Li-Jia
LJ
Song
Ye
Y
Tao
Qiang
Q
Meng
Qian-Li
QL
Yang
Guo-Dong
GD
Gao
Hua
H
Zhang
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism*; D006801:Humans; D008297:Male; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D013702:Temporal Lobe / Q000378:metabolism
D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; C406962:SLC16A4 protein, human; C516342:Slc16a3 protein, rat