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Evidence suggests that lactate could be a preferential energy substrate transferred from astrocytes to neurons. Such a process implies the presence of specific monocarboxylate transporters on both cell types. Expression of MCT1 and MCT2, two isoforms of the monocarboxylate transporter (MCT) family, was studied in enriched cultures of mouse cortical astrocytes or neurons. It was observed that, at both the mRNA and the protein levels, astrocytes strongly expressed MCT1 but had very little if any MCT2. By contrast, neurons had high amounts of MCT2 mRNA, although MCT1 mRNA was also detected. Double immunofluorescent labelings with appropriate markers confirmed the cell-specific preference in the expression of MCT1 and MCT2, but they revealed that a subset of neurons expresses low to moderate levels of MCT1. Parallel immunocytochemical stainings of cultured neurons with the presynaptic marker synaptophysin showed that MCT2 expression is correlated with synaptic development. Although MCT2 and synaptophysin were not colocalized, their distribution was similar, and they were often closely apposed, suggesting that MCT2 could be associated with postsynaptic terminals. Interaction between astrocytes and neurons, as occurring in layered cultures, did not modify the levels of MCT1 and MCT2 expression or their distribution and cell-specific preference under the conditions used. However, a close apposition between neurites and MCT1-expressing astrocytic processes was apparent and developed as cultures evolved. In addition to providing an extensive description of MCT distribution in cultured cells, our data underscore the potential of such preparations for future studies on the regulation of MCT expression.

Regulation of the expression of MCT1 and MCT2, two isoforms of the monocarboxylate transporter (MCT) family, was investigated in primary cultures of mouse cortical neurons. Under basal conditions, both MCT immunoreactivities (IR) were found in the cell soma and dendrites, although IR for MCT1 appeared less bright than for MCT2. Treatment of cultured cortical neurons with 100 lM noradrenaline (NA) led, after a few hours, to a striking enhancement in fluorescence intensity associated with MCT2 IR in the cell soma as well as in dendrites. In contrast, MCT1 IR was not altered by NA treatment. Western blot experiments performed on cultured neurons treated with NA confirmed that MCT2 protein expression was increased. Forskolin and dBcAMP also enhanced MCT2 expression, suggesting the implication of a cAMP-mediated pathway in the effect of NA. Surprisingly, neither NA, dBcAMP nor forskolin affected MCT2 mRNA expression. Application of cycloheximide, a protein synthesis inhibitor, prevented the enhancement of MCT2 IR, while the mRNA synthesis inhibitor actinomycin D also blocked the effect of NA on MCT2 IR levels. These results suggest that regulation of MCT2 expression in neurons by NA occurs at the translational level despite the requirement for an as yet unknown transcriptional step.

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