Glucose transporter 1 facilitates glucose transport across the blood–brain barrier. By increasing histone acetylation at the SLC2A1 promotor, valproic acid could increase SLC2A1 gene expression. This study was designed to evaluate the effects of valproic acid on glucose transport in astrocyte cultures derived from SLC2A1 heterozygous mice. Primary astrocyte cultures were prepared from the cerebral cortex of 1-day-old neonatal mice. Cultured astrocytes were incubated with valproic acid (0.05, 0.5, and 5 mM) for 48 hours. On day 3, the glucose uptake capacity of the astrocytes was measured by using 14C-2-Deoxy-d-glucose under zero-trans conditions. The heterozygous astrocyte glucose uptake treated with valproic acid (0.05 and 0.5 mM) for 48 hours was significantly increased compared with the untreated control heterozygous astrocytes. Our findings demonstrate that valproic acid increased glucose transport capacity in SLC2A1 heterozygous cerebral astrocytes.
DickAPHarikSIKlipAWalkerDM. Identification and characterization of the glucose transporter of the blood-brain barrier by cytochalasin B binding and immunological reactivity. Proc Natl Acad Sci U S A. 1984;81:7233–7237.
2.
De VivoDCTrifilettiRRJacobsonRIRonenGMBehmandRAHarikSI. Defective glucose transport across the blood-brain barrier as a cause of persistent hypoglycorrhachia, seizures, and developmental delay. N Engl J Med. 1991;325:703–709.
3.
BrockmannKWangDKorenkeCG. Autosomal dominant glut-1 deficiency syndrome and familial epilepsy. Ann Neurol. 2001;50:476–485.
4.
WangDPascualJMYangH. Glut-1 deficiency syndrome: clinical, genetic, and therapeutic aspects. Ann Neurol. 2005;57:111–118.
5.
SeidnerGAlvarezMGYehJI. GLUT-1 deficiency syndrome caused by haploinsufficiency of the blood-brain barrier hexose carrier. Nat Genet. 1998;18:188–191.
6.
KlepperJGarcia-AlvarezMO'DriscollKR. Erythrocyte 3-O-methyl-D-glucose uptake assay for diagnosis of glucose-transporter-protein syndrome. J Clin Lab Anal. 1999;13:116–121.
7.
KlepperJWangDFischbargJ. Defective glucose transport across brain tissue barriers: a newly recognized neurological syndrome. Neurochem Res. 1999;24:587–594.
8.
WangDKranz-EblePDe VivoDC. Mutational analysis of GLUT1 (SLC2A1) in Glut-1 deficiency syndrome. Hum Mutat. 2000;16:224–231.
9.
MuecklerMCarusoCBaldwinSA. Sequence and structure of a human glucose transporter. Science. 1985;229:941–945.
LangePGertsenEMondenIKlepperJKellerK. Functional consequences of an in vivo mutation in exon 10 of the human GLUT1 gene. FEBS Lett. 2003;555:274–278.
12.
FriedmanJRThieleEAWangD. Atypical GLUT1 deficiency with prominent movement disorder responsive to ketogenic diet. Mov Disord. 2006;21:241–245.
13.
Kulikova-SchupakRHoYKranz-EblePYangHWangDDe VivoDC. Stimulation of GLUT-1 gene transcription by thioctic acid and its potential therapeutic value in Glut-1 deficiency syndrome (GLUT-1DS). J Inherit Metab Dis. 2001;24:S106.
14.
LearyLDWangDNordliDRJrEngelstadKDe VivoDC. Seizure characterization and electroencephalographic features in Glut-1 deficiency syndrome. Epilepsia. 2003;44:701–707.
15.
PhielCJZhangFHuangEYGuentherMGLazarMAKleinPS. Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen. J Biol Chem. 2001;276:36734–36741.
16.
GottlicherMMinucciSZhuP. Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells. EMBO J. 2001;20:6969–6978.
17.
FanSMaguireCARamirezSH. Valproic acid enhances gene expression from viral gene transfer vectors. J Virol Methods. 2005;125:23–33.
18.
EyalSYagenBSobolEAltschulerYShmuelMBialerM. The activity of antiepileptic drugs as histone deacetylase inhibitors. Epilepsia. 2004;45:737–744.
19.
KellyWKO'ConnorOAMarksPA. Histone deacetylase inhibitors: from target to clinical trials. Expert Opin Investig Drugs. 2002;11:1695–1713.
20.
Van LintCEmilianiSVerdinE. The expression of a small fraction of cellular genes is changed in response to histone hyperacetylation. Gene Expr. 1996;5:245–253.
21.
WangDPascualJMYangH. A mouse model for Glut-1 haploinsufficiency. Hum Mol Genet. 2006;15:1169–1179.
22.
WarnerAPriviteraMBatesD. Standards of laboratory practice: antiepileptic drug monitoring. National Academy of Clinical Biochemistry. Clin Chem. 1998;44:1085–1095.
23.
ChangRCStadlinATsangD. Effects of tumor necrosis factor alpha on taurine uptake in cultured rat astrocytes. Neurochem Int. 2001;38:249–254.
24.
NagamatsuSNakamichiYInoueNInoueMNishinoHSawaH. Rat C6 glioma cell growth is related to glucose transport and metabolism. Biochem J. 1996;319(pt 2):477–482.
25.
KielbSKooHPBloomDAFaerberGJ. Nephrolithiasis associated with the ketogenic diet. J Urol. 2000;164:464–466.
26.
StewartWAGordonKCamfieldP. Acute pancreatitis causing death in a child on the ketogenic diet. J Child Neurol. 2001;16:682.
27.
BestTHFranzDNGilbertDLNelsonDPEpsteinMR. Cardiac complications in pediatric patients on the ketogenic diet. Neurology. 2000;54:2328–2330.
28.
Berry-KravisEBoothGTaylorAValentinoLA. Bruising and the ketogenic diet: evidence for diet-induced changes in platelet function. Ann Neurol. 2001;49:98–103.
29.
HoytCSBillsonFA. Optic neuropathy in ketogenic diet. Br J Ophthalmol. 1979;63:191–194.
30.
HaspelHCStephensonKNDavies-HillT. Effects of barbiturates on facilitative glucose transporters are pharmacologically specific and isoform selective. J Membr Biol. 1999;169:45–53.
31.
HonkanenRAMcBathHKushmerickC. Barbiturates inhibit hexose transport in cultured mammalian cells and human erythrocytes and interact directly with purified GLUT-1. Biochemistry. 1995;34:535–544.
32.
KlepperJFlorckenAFischbargJVoitT. Effects of anticonvulsants on GLUT1-mediated glucose transport in GLUT1 deficiency syndrome in vitro. Eur J Pediatr. 2003;162:84–89.
33.
DuelliRKuschinskyW. Brain glucose transporters: relationship to local energy demand. News Physiol Sci. 2001;16:71–76.
34.
YuSDingWG. The 45 kDa form of glucose transporter 1 (GLUT1) is localized in oligodendrocyte and astrocyte but not in microglia in the rat brain. Brain Res. 1998;797:65–72.
35.
MieleCFormisanoPCondorelliG. Abnormal glucose transport and GLUT1 cell-surface content in fibroblasts and skeletal muscle from NIDDM and obese subjects. Diabetologia. 1997;40:421–429.
36.
NightingaleKPO'NeillLPTurnerBM. Histone modifications: signalling receptors and potential elements of a heritable epigenetic code. Curr Opin Genet Dev. 2006;16:125–136.
37.
RothSYDenuJMAllisCD. Histone acetyltransferases. Annu Rev Biochem. 2001;70:81–120.
38.
RonenGMBuckleyDPenneySStreinerDL. Long-term prognosis in children with neonatal seizures: a population-based study. Neurology. 2007;69:1816–1822.
39.
BhallaKN. Epigenetic and chromatin modifiers as targeted therapy of hematologic malignancies. J Clin Oncol. 2005;23:3971–3993.
40.
SumnerCJHuynhTNMarkowitzJA. Valproic acid increases SMN levels in spinal muscular atrophy patient cells. Ann Neurol. 2003;54:647–654.
41.
MaherJRonenGMOgunyemiAOGouldenKJ. Occipital paroxysmal discharges suppressed by eye opening: variability in clinical and seizure manifestations in childhood. Epilepsia. 1995;36:52–57.
