MCT2 is a Major Neuronal Monocarboxylate Transporter in the Adult Mouse Brain

Abstract

Although previous Northern blot and in situ hybridization studies suggested that neurons express the monocarboxylate transporter MCT2, subsequent immunohistochemical analyzes either failed to confirm the presence of this transporter or revealed only a low density of immunolabeled neuronal processes in vivo. The authors report that appropriate section pretreatment (brief warming episode or proteinase K exposure) leads to extensive labeling of the neuropil, which appears as tiny puncta throughout the whole mouse brain. In addition, intense MCT2 immunoreactivity was found in cerebellar Purkinje cell bodies and their processes, on mossy fibers in the cerebellum, and on sensory fibers in the brainstem. Double immunofluorescent labeling with appropriate markers and observation with epifluorescence and confocal microscopy did not show extensive colocalization of MCT2 immunoreactivity with presynaptic or postsynaptic elements, but colocalization could be observed occasionally in the cortex with the postsynaptic density protein PSD95. Observations made at the electron microscopic level in the cortex corroborated these results and showed that MCT2 immunoreactivity was associated with wide membrane segments of neuronal processes. These data provide convincing evidence that MCT2 represents a major neuronal monocarboxylate transporter in the adult mouse brain, and further suggest that mature neurons could use monocarboxylates such as lactate as additional energy substrates.

Ex Vivo Analysis of Lactate and Glucose Metabolism in the Rat Brain under Different States of Depressed Activity

“…Measurements were performed at 30°C. Proton-decoupled 13 C-NMR spectra of perchloric acid extracts were acquired under the conditions of a 5.1-s pulse (ϳ52°flip angle), 1.18-s acquisition time, 0.1-s relaxation delay, 22,150 Hz sweep width, 64K memory, gated proton composite pulse decoupling, and D 2 O lock. The number of scans was 50,000.…”

“…The acquisition sequences involved a proton spin echo with calibrated 90 and 180°pulses separated by a 3.94-ms delay corresponding to the 0.5 J CH value for the 1 H-13 C scalar coupling in amino acid -CH 2 -and -CH 3 (J CH ϭ 126 -132 Hz) either with or without 13 C spin inversion with a 90, 120, 120, and 90°composite pulse (8.75 s for 90°flip angle). Other parameters were a 3.28-s acquisition time, 8-s relaxation delay, 5,000 Hz sweep width, and 32K memory size.…”

“…The proposed astrocyte-neuron lactate shuttle hypothesis (ANLSH) 1 (1) as the coupling model between neuronal activity and energy metabolism requires the involvement of different components, the occurrence and localization of which have been investigated analytically at the molecular level, i.e. glutamate transporter and Na ϩ ,K ϩ -ATPase (11), lactate dehydrogenase isoenzymes (12), and monocarboxylate transporters (13,14). Although brain lactate production and lactate use by neurons as an energy source are widely admitted, the relevance of the coupling model, particularly the neuronal utilization of glia-produced lactate, is a topical issue (15, 16).…”

“…This was particularly important for glucose and lactate because of anaerobic glycolysis. To control this process, we determined the time dependence of brain glucose, lactate, and amino acid content and 13 C-enrichments after blood circulation arrest. Thus, comparing alanine and lactate enrichments under the different conditions confirmed the compartmentation of their metabolism.…”

Enhanced Cerebral Expression of MCT1 and MCT2 in a Rat Ischemia Model Occurs in Activated Microglial Cells

“…MCT1 is predominantly found on endothelial cells forming cerebral blood vessels as well as on astrocytes (Gerhart et al, 1997;Hanu et al, 2000;Pierre et al, 2000). MCT4 is exclusively expressed by astrocytes (Rafiki et al, 2003;, whereas MCT2 constitutes the main neuronal MCT (Pierre et al, 2002;Debernardi et al, 2003). So far, few studies have investigated the cellular changes of cerebral MCT expression occurring after ischemia.…”