Cellular and subcellular distribution of monocarboxylate transporters in cultured brain cells and in the adult brain

被引:198
作者
Pellerin, L
Halestrap, AP
Pierre, K
机构
[1] Univ Lausanne, Dept Physiol, CH-1015 Lausanne, Switzerland
[2] Univ Bristol, Dept Biochem, Bristol BS8 1TH, Avon, England
关键词
lactate; astrocyte; MCT1; MCT2; MCT4;
D O I
10.1002/jnr.20307
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Monocarboxylate transporters (MCTs) are involved in the uptake and release of lactate, pyruvate, and ketone bodies. Studies of their distribution at both the mRNA and protein levels have highlighted the specific expression of MCT1, MCT2, and more recently MCT4 in the central nervous system. MCT1 was found strongly expressed by cortical astrocytes both in vitro and in vivo. It was also found at high levels on blood vessels, ependymocytes, and glia limitans. A subset of neurons in vitro exhibited a weak but significant MCT1 expression. In contrast, it was determined that MCT2 represents the predominant neuronal MCT on cultured neurons as well as on neurons throughout the brain parenchyma. At the subcellular level, part of MCT2 is located in postsynaptic densities. Specific populations of astrocytes in the white matter also exhibited MCT2 expression in the rat, but not in the mouse brain. MCT4 was found exclusively in astrocytes in several areas including the cortex, the hippocampus, and the cerebellum. MCT2 expression increased in cultured neurons with days in vitro commensurate with increased synapse formation. Moreover, a significant increase in MCT2 expression was observed in cultured neurons exposed to noradrenaline, an effect involving a regulation at the translational level. The description of MCTs on different cell types in the central nervous system together with clear evidence for regulation of their expression further emphasize the important role that monocarboxylates, and particularly lactate, might play in brain energy metabolism not only during development but also in the adult. (C) 2004 Wiley-Liss, Inc.
引用
收藏
页码:55 / 64
页数:10
相关论文
共 76 条
[1]   Striking differences in glucose and lactate levels between brain extracellular fluid and plasma in conscious human subjects: Effects of hyperglycemia and hypoglycemia [J].
Abi-Saab, WM ;
Maggs, DG ;
Jones, T ;
Jacob, R ;
Srihari, V ;
Thompson, J ;
Kerr, D ;
Leone, P ;
Krystal, JH ;
Spencer, DD ;
During, MJ ;
Sherwin, RS .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2002, 22 (03) :271-279
[2]   Dynamic imaging of free cytosolic ATP concentration during fuel sensing by rat hypothalamic neurones:: evidence for ATP-independent control of ATP-sensitive K+ channels [J].
Ainscow, EK ;
Mirshamsi, S ;
Tang, T ;
Ashford, MLJ ;
Rutter, GA .
JOURNAL OF PHYSIOLOGY-LONDON, 2002, 544 (02) :429-445
[3]   Perinatal and early postnatal changes in the expression of monocarboxylate transporters MCT1 and MCT2 in the rat forebrain [J].
Baud, O ;
Fayol, L ;
Gressens, P ;
Pellerin, L ;
Magistretti, P ;
Evrard, P ;
Verney, C .
JOURNAL OF COMPARATIVE NEUROLOGY, 2003, 465 (03) :445-454
[4]   Immunogold cytochemistry identifies specialized membrane domains for monocarboxylate transport in the central nervous system [J].
Bergersen, L ;
Rafiki, A ;
Ottersen, OP .
NEUROCHEMICAL RESEARCH, 2002, 27 (1-2) :89-96
[5]   A novel postsynaptic density protein:: the monocarboxylate transporter MCT2 is co-localized with δ-glutamate receptors in postsynaptic densities of parallel fiber-Purkinje cell synapses [J].
Bergersen, L ;
Wærhaug, O ;
Helm, J ;
Thomas, M ;
Laake, P ;
Davies, AJ ;
Wilson, MC ;
Halestrap, AP ;
Ottersen, OP .
EXPERIMENTAL BRAIN RESEARCH, 2001, 136 (04) :523-534
[6]  
BERGERSEN L, 2004, IN PRESS CEREB CORTE
[7]   The concept of maximal lactate steady state - A bridge between biochemistry, physiology and sport science [J].
Billat, VL ;
Sirvent, P ;
Py, G ;
Koralsztein, JP ;
Mercier, J .
SPORTS MEDICINE, 2003, 33 (06) :407-426
[8]   Dual-gene, dual-cell type therapy against an excitotoxic insult by bolstering neuroenergetics [J].
Bliss, TM ;
Ip, M ;
Cheng, E ;
Minami, M ;
Pellerin, L ;
Magistretti, P ;
Sapolsky, RM .
JOURNAL OF NEUROSCIENCE, 2004, 24 (27) :6202-6208
[9]   Developmental and hormonal regulation of the monocarboxylate transporter 2 (MCT2) expression in the mouse germ cells [J].
Boussouar, F ;
Mauduit, C ;
Tabone, E ;
Pellerin, L ;
Magistretti, PJ ;
Benahmed, M .
BIOLOGY OF REPRODUCTION, 2003, 69 (03) :1069-1078
[10]   The metabolism of [3-13C]lactate in the rat brain is specific of a pyruvate carboxylase-deprived compartment [J].
Bouzier, AK ;
Thiaudiere, E ;
Biran, M ;
Rouland, R ;
Canioni, P ;
Merle, M .
JOURNAL OF NEUROCHEMISTRY, 2000, 75 (02) :480-486