Monocarboxylate transporters in the central nervous system: distribution, regulation and function

Abstract

Monocarboxylate transporters (MCTs) are proton-linked membrane carriers involved in the transport of monocarboxylates such as lactate, pyruvate, as well as ketone bodies. They belong to a larger family of transporters composed of 14 members in mammals based on sequence homologies. MCTs are found in various tissues including the brain where three isoforms, MCT1, MCT2 and MCT4, have been described. Each of these isoforms exhibits a distinct regional and cellular distribution in rodent brain. At the cellular level, MCT1 is expressed by endothelial cells of microvessels, by ependymocytes as well as by astrocytes. MCT4 expression appears to be specific for astrocytes. By contrast, the predominant neuronal monocarboxylate transporter is MCT2. Interestingly, part of MCT2 immunoreactivity is located at postsynaptic sites, suggesting a particular role of monocarboxylates and their transporters in synaptic transmission. In addition to variation in expression during development and upon nutritional modifications, new data indicate that MCT expression is regulated at the translational level by neurotransmitters. Understanding how transport of monocarboxylates is regulated could be of particular importance not only for neuroenergetics but also for areas such as functional brain imaging, regulation of food intake and glucose homeostasis, or for central nervous system disorders such as ischaemia and neurodegenerative diseases.

Brain edema in acute liver failure and chronic liver disease: Similarities and differences

“…Lactate is produced from pyruvate by both astrocytes and neurons via the action of lactate dehydrogenase (LDH). However, astrocytes have been shown to be much more glycolytic than neurons, and thus produce large amounts of lactate via LDH-5 (astrocytic isoform), which is then expelled into the extracellular space through monocarboxylate transporters 1 and 4 (Pierre and Pellerin, 2005). Lactate can then be taken up by neurons via monocarboxylate transporters 2, and used as an energy substrate entering the tricarboxylic acid cycle through its conversion into pyruvate by neuronal LDH-1.…”

Physiological glucose is critical for optimized neuronal viability and AMPK responsiveness in vitro

“…In addition to glucose, other fuels such as lactate, pyruvate, fatty acids, and ketone bodies have been shown to play roles in neuronal energy metabolism both in vivo and in vitro [reviewed in (Pierre, et al, 2005)] (Morgan, et al, 2004). Although the system presented in this paper is simplified, as we chose to focus on only glucose to limit the variables, we recognize the importance of other nutrients to neuronal metabolism.…”

Prostaglandin transporter expression in mouse brain during development and in response to hypoxia

“…It is possible therefore that the decreased neuronal PGT expression during hypoxia might be the result of a negative feedback to lower the PGTs since lactate would be increased. However, it is also possible that the monocarboxylate transporters (Pierre and Pellerin, 2005;Ullah et al, 2006) could be increased to alleviate the intracellular lactate load. In that case, the explanation for the neuronal decrease in PGTs during hypoxia may not be apparent at present.…”