Distribution of the monocarboxylate transporter MCT2 in human cerebral cortex: An immunohistochemical study

被引:23
作者
Chiry, Oriana [2 ,3 ]
Fishbein, William N. [4 ]
Merezhinskaya, Natalya [4 ]
Clarke, Stephanie [1 ,5 ]
Galuske, Ralf [2 ,3 ]
Magistretti, Pierre J. [1 ,6 ,7 ]
Pellerin, Luc [1 ]
机构
[1] Univ Lausanne, Dept Physiol, CH-1005 Lausanne, Switzerland
[2] Max Planck Inst Brain Res, D-60528 Frankfurt, Germany
[3] Tech Univ Darmstadt, Inst Zool, D-64287 Darmstadt, Germany
[4] Armed Forces Inst Pathol, Biochem Pathol Div, Environm & Toxicol Pathol Dept, Washington, DC 20306 USA
[5] Univ Lausanne, CHUV, Serv Neuropsychol & Neurorehabil, CH-1011 Lausanne, Switzerland
[6] CHU Vaudois, Ctr Psychiat Neurosci, CH-1011 Lausanne, Switzerland
[7] Ecole Polytech Fed Lausanne, Brain Mind Inst, CH-1015 Lausanne, Switzerland
关键词
energy metabolism; lactate; postsynaptic density; neuron; astrocyte; astrocyte-neuron lactate shuttle;
D O I
10.1016/j.brainres.2008.06.025
中图分类号
Q189 [神经科学];
学科分类号
071006 [神经生物学];
摘要
The monocarboxylate transporter MCT2 belongs to a large family of membrane proteins involved in the transport of lactate, pyruvate and ketone bodies. Although its expression in rodent brain has been well documented, the presence of MCT2 in the human brain has been questioned on the basis of low mRNA abundance. In this study, the distribution of the monocarboxylate transporter MCT2 has been investigated in the cortex of normal adult human brain using an immunohistochemical approach. Widespread neuropil staining in all cortical layers was observed by light microscopy. Such a distribution was very similar in three different cortical areas investigated. At the cellular level, the expression of MCT2 could be observed in a large number of neurons, in fibers both in grey and white matter, as well as in some astrocytes, mostly localized in layer I and in the white matter. Double staining experiments combined with confocal microscopy confirmed the neuronal expression but also suggested a preferential postsynaptic localization of synaptic MCT2 expression. A few astrocytes in the grey matter appeared to exhibit MCT2 labelling but at low levels. Electron microscopy revealed strong MCT2 expression at asymmetric synapses in the postsynaptic density and also within the spine head but not in the presynaptic terminal. These data not only demonstrate neuronal MCT2 expression in human, but since a portion of it exhibits a distinct synaptic localization, it further supports a putative role for MCT2 in adjustment of energy supply to levels of activity. (C) 2008 Elsevier B.V. All rights reserved.
引用
收藏
页码:61 / 69
页数:9
相关论文
共 38 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]
Brain lactate kinetics: Modeling evidence for neuronal lactate uptake upon activation [J].
Aubert, A ;
Costalat, R ;
Magistretti, PJ ;
Pellerin, L .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (45) :16448-16453
[3]
A coherent neurobiological framework for functional neuroimaging provided by a model integrating compartmentalized energy metabolism [J].
Aubert, Agnes ;
Pellerin, Luc ;
Magistretti, Pierre J. ;
Costalat, Robert .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (10) :4188-4193
[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]
Selective postsynaptic co-localization of MCT2 with AMPA receptor GluR2/3 subunits at excitatory synapses exhibiting AMPA receptor trafficking [J].
Bergersen, LH ;
Magistretti, PJ ;
Pellerin, L .
CEREBRAL CORTEX, 2005, 15 (04) :361-370
[7]
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
[8]
Characterization of the high-affinity monocarboxylate transporter MCT2 in Xenopus laevis oocytes [J].
Bröer, S ;
Bröer, A ;
Schneider, HP ;
Stegen, C ;
Halestrap, AP ;
Deitmer, JW .
BIOCHEMICAL JOURNAL, 1999, 341 :529-535
[9]
Insulin and IGF-1 enhance the expression of the neuronal monocarboxylate transporter MCT2 by translational activation via stimulation of the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin pathway [J].
Chenal, Julie ;
Pierre, Karin ;
Pellerin, Luc .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2008, 27 (01) :53-65
[10]
Noradrenaline enhances the expression of the neuronal monocarboxylate transporter MCT2 by translational activation via stimulation of PI3K/Akt and the mTOR/S6K pathway [J].
Chenal, Julie ;
Pellerin, Luc .
JOURNAL OF NEUROCHEMISTRY, 2007, 102 (02) :389-397