Expression of monocarboxylate transporter mRNAs in mouse brain: Support for a distinct role of lactate as an energy substrate for the neonatal vs. adult brain

Abstract

Under particular circumstances like lactation and fasting, the blood-borne monocarboxylates acetoacetate, ␤-hydroxybutyrate, and lactate represent significant energy substrates for the brain. Their utilization is dependent on a transport system present on both endothelial cells forming the blood-brain barrier and on intraparenchymal brain cells. Recently, two monocarboxylate transporters, MCT1 and MCT2, have been cloned. We report here the characterization by Northern blot analysis and by in situ hybridization of the expression of MCT1 and MCT2 mRNAs in the mouse brain. In adults, both transporter mRNAs are highly expressed in the cortex, the hippocampus and the cerebellum. During development, a peak in the expression of both transporters occurs around postnatal day 15, declining rapidly by 30 days at levels observed in adults. Double-labeling experiments reveal that the expression of MCT1 mRNA in endothelial cells is highest at postnatal day 15 and is not detectable at adult stages. These results support the notion that monocarboxylates are important energy substrates for the brain at early postnatal stages and are consistent with the sharp decrease in blood-borne monocarboxylate utilization after weaning. In addition, the observation of a sustained intraparenchymal expression of monocarboxylate transporter mRNAs in adults, in face of the seemingly complete disappearance of their expression on endothelial cells, reinforces the view that an intercellular exchange of lactate occurs within the adult brain.Glucose is the major, if not exclusive, energy substrate for the brain (1). Under certain situations, other substrates can contribute significantly to brain energy demands. Thus, immediately after birth, lactate present in high amounts in the blood following delivery provides an important source of energy for the brain in the presuckling period (2, 3). In addition, acetoacetate and ␤-hydroxybutyrate, two ketone bodies formed by the hepatic oxidation of fat contained in maternal milk, are also significant energy substrates for the brain during the preweaning period (4, 5). These energy substrates however do not cross the blood-brain barrier easily, and require a transport system to reach the brain parenchyma. Such a transport system that has been demonstrated by uptake studies with tracers across the blood-brain barrier during lactation is shared by lactate, pyruvate, and the ketone bodies (6, 7).Recently, two transporters for monocarboxylates have been cloned and their distribution in various tissues, organs, and cell types has been described (8-10). These reports made limited mention about their presence in the central nervous system, despite evidence from functional studies for the presence of a lactate transport system in different brain cell types or in tissue slices (11)(12)(13)(14). More recently, two reports have appeared, describing the presence of monocarboxylate transporters (MCT) mRNAs by Northern blot analysis (15) as well as the MCT1 protein (16) in the central nervous system. In this article...

Physiological and Molecular Characteristics of Rat Hypothalamic Ventromedial Nucleus Glucosensing Neurons

“…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). Results for other mRNAs might also reflect the developmental stage of these young animals.…”

Added astroglia promote greater synapse density and higher activity in neuronal networks

“…The glucose-lactate shuttle between astrocytes and neurons enables more efficient energy handling (Pellerin et al, 1998) because synapse distance varies from the capillary supply of glucose and removal of lactate, but astrocytes maintain close contact to capillaries in vivo. Most intriguing is the recent discovery of synaptic transmission onto astroglia through astroglial Glu-R1 (AMPA) receptors and GABA A receptors (Jabs et al, 2005).…”

Cellular mechanisms of brain energy metabolism and their relevance to functional brain imaging

“…Further support for this notion of an`astrocyte^neuron lactate shuttle' in the brain (¢gure 2b), has been provided by the recent identi¢-cation of two lactate transporters, MCT-1 and MCT-2, which are present in the central nervous system (Pellerin et al 1998) and selectively expressed in astrocytes or neurons. Thus, MCT-1 is enriched in astrocytes in culture while MCT-2 is predominantly expressed in neurons (BrÎer et al 1997).…”