Expression of monocarboxylate transporter mRNAs in mouse brain: Support for a distinct role of lactate as an energy substrate for the neonatal vs. adult brain

被引:243
作者
Pellerin, L
Pellegri, G
Martin, JL
Magistretti, PJ
机构
[1] Univ Lausanne, Fac Med, Inst Physiol, CH-1005 Lausanne, Switzerland
[2] Univ Lausanne, Fac Med, CHU Vaudois, Serv Neurol,Lab Rech, CH-1005 Lausanne, Switzerland
关键词
D O I
10.1073/pnas.95.7.3990
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Under particular circumstances like lactation and fasting the blood-borne monocarboxylates acetoacetate, beta-hydroxybutyrate, and lactate represent significant energy substrates for the brain. Their utilization Is dependent on a transport system present on both endothelial cells forming the blood-brain barrier and on intraparenchymal brain cells. Recently, two monocarboxylate transporters, MCT1 and MCT2, have been cloned. We report here the characterization by Northern blot analysis and by in situ hybridization of the expression of MCT1 and MCT2 mRNAs in the mouse brain. In adults, both transporter mRNAs are highly expressed in the cortex, the hippocampus and the cerebellum. During development, a peak in the expression of both transporters occurs around postnatal day 15, declining rapidly by 30 days at levels observed in adults. Double-labeling experiments reveal that the expression of MCT1 mRNA in endothelial cells is highest at postnatal day 15 and is not detectable at adult stages. These results support the notion that monocarboxylates are important energy substrates for the brain at early postnatal stages and are consistent with the sharp decrease in blood-borne monocarboxylate utilization after weaning. In addition, the observation of a sustained intraparenchymal expression of monocarboxylate transporter mRNAs in adults, in face of the seemingly complete disappearance of their expression on endothelial cells, reinforces the view that an intercellular exchange of lactate occurs within the adult brain.
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页码:3990 / 3995
页数:6
相关论文
共 46 条
[1]   LACTATE COMPARTMENTATION IN HIPPOCAMPAL SLICES - EVIDENCE FOR A TRANSPORTER [J].
ASSAF, HM ;
RICCI, AJ ;
WHITTINGHAM, TS ;
LAMANNA, JC ;
RATCHESON, RA ;
LUST, WD .
METABOLIC BRAIN DISEASE, 1990, 5 (03) :143-154
[2]   Selective distribution of lactate dehydrogenase isoenzymes in neurons and astrocytes of human brain [J].
Bittar, PG ;
Charnay, Y ;
Pellerin, L ;
Bouras, C ;
Magistretti, PJ .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 1996, 16 (06) :1079-1089
[3]   Comparison of lactate transport in astroglial cells and monocarboxylate transporter 1 (MCT 1) expressing Xenopus laevis oocytes - Expression of two different monocarboxylate transporters in astroglial cells and neurons [J].
Broer, S ;
Rahman, B ;
Pellegri, G ;
Pellerin, L ;
Martin, JL ;
Verleysdonk, S ;
Hamprecht, B ;
Magistretti, PJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (48) :30096-30102
[4]   Cloning and sequencing of the monocarboxylate transporter from mouse Ehrlich Lettre tumour cell confirms its identity as MCT1 and demonstrates that glycosylation is not required for MCT1 function [J].
Carpenter, L ;
Poole, RC ;
Halestrap, AP .
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 1996, 1279 (02) :157-163
[5]   ISOLATION OF BIOLOGICALLY-ACTIVE RIBONUCLEIC-ACID FROM SOURCES ENRICHED IN RIBONUCLEASE [J].
CHIRGWIN, JM ;
PRZYBYLA, AE ;
MACDONALD, RJ ;
RUTTER, WJ .
BIOCHEMISTRY, 1979, 18 (24) :5294-5299
[6]  
Clarke Donald D., 1994, P645
[7]   KINETICS OF BLOOD-BRAIN-BARRIER TRANSPORT OF PYRUVATE, LACTATE AND GLUCOSE IN SUCKLING, WEANLING AND ADULT-RATS [J].
CREMER, JE ;
CUNNINGHAM, VJ ;
PARDRIDGE, WM ;
BRAUN, LD ;
OLDENDORF, WH .
JOURNAL OF NEUROCHEMISTRY, 1979, 33 (02) :439-445
[8]   INHIBITION, BY 2-OXO ACIDS THAT ACCUMULATE IN MAPLE-SYRUP-URINE DISEASE, OF LACTATE, PYRUVATE, AND 3-HYDROXYBUTYRATE TRANSPORT ACROSS THE BLOOD-BRAIN-BARRIER [J].
CREMER, JE ;
TEAL, HM ;
CUNNINGHAM, VJ .
JOURNAL OF NEUROCHEMISTRY, 1982, 39 (03) :674-677
[9]   SUBSTRATE UTILIZATION AND BRAIN-DEVELOPMENT [J].
CREMER, JE .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 1982, 2 (04) :394-407
[10]   LACTATE, 3-HYDROXYBUTYRATE, AND GLUCOSE AS SUBSTRATES FOR THE EARLY POSTNATAL RAT-BRAIN [J].
DOMBROWSKI, GJ ;
SWIATEK, KR ;
CHAO, KL .
NEUROCHEMICAL RESEARCH, 1989, 14 (07) :667-675