Cell‐specific expression pattern of monocarboxylate transporters in astrocytes and neurons observed in different mouse brain cortical cell cultures

Abstract

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.

Physiological and Molecular Characteristics of Rat Hypothalamic Ventromedial Nucleus Glucosensing Neurons

“…Here, about half of all VMN neurons, regardless of their glucosensing properties, expressed MCT-1, whereas a much smaller number expressed MCT-2. This finding is contrary to prior reports in adult and neonatal rat and mouse brains (44,79,80). Our current findings for MCTs might be influenced by our use of 14-to 21-day-old pups, as the expression of MCT-1 mRNA is highest at postnatal day 15 (81).…”

“…Lactate, produced largely by astrocytes (42), and ketone bodies from the periphery can serve as alternate energy sources or signaling molecules to glucose once it is transported into neurons by monocarboxylate transporters (MCTs) (43). Current evidence suggests that neurons express mainly the MCT-2 isoform (44).…”

Prion Protein Regulates Glutamate-Dependent Lactate Transport of Astrocytes

“…It has been shown that the ␣2-and ␤2-ATPase are expressed by glial cells, in particular by astrocytes (Peng et al, 1997). Predominantly or even exclusively expressed in astrocytes are also the monocarboxylate transporters MCT1 and MCT4 (Debernardi et al, 2003), which interact with basigin and are regulated in their activity by basigin. Because ␣2/␤2-ATPase interacts with basigin and PrP, PrP may be involved in the regulation of the glial ␣2/ ␤2-ATPase pump activity and transport of lactate.…”

Inhibition of Monocarboxylate Transporter 2 in the Retrotrapezoid Nucleus in Rats: A Test of the Astrocyte–Neuron Lactate-Shuttle Hypothesis

“…A family of MCTs transports lactate, pyruvate, and ketone bodies across biological membranes (Halestrap and Price, 1999), and MCT1, MCT2, and MCT4 have been identified in the CNS. MCT1 and MCT4 are expressed in astrocytes, and MCT2 is expressed in neurons (Bröer et al, 1997;Gerhart et al, 1997;Pierre et al, 2002;Debernardi et al, 2003). Because MCT2 has a lower K m for lactate (ϳ0.7 mM) than the K m for either MCT1 or MCT4 (ϳ5-7 and 28 -35 mM, respectively) (Bröer et al, 1997(Bröer et al, , 1999Poole and Halestrap, 1997;Halestrap and Price, 1999;Manning Fox et al, 2000), the cell-specific distribution of these transporters between astrocytes and neurons seems designed to move lactate from astrocytes to neurons.…”