Mounting evidence from in vitro experiments indicates that lactate is an efficient energy substrate for neurons and that it may significantly contribute to maintain synaptic transmission, particularly during periods of intense activity. Since lactate does not cross the blood-brain barrier easily, blood-borne lactate cannot be a significant source. In vitro studies by several laboratories indicate that astrocytes release large amounts of lactate. In 1994, we proposed a mechanism whereby lactate could be produced by astrocytes in an activity-dependent, glutamate-mediated manner. Over the last 2 years we have obtained further evidence supporting the notion that a transfer of lactate from astrocytes to neurons might indeed take place. In this article, we first review data showing the presence of mRNA encoding for two monocarboxylate transporters, MCT1 and MCT2, in the adult mouse brain. Second, by using monoclonal antibodies selectively directed against the two distinct lactate dehydrogenase isoforms, LDH₁ and LDH₅, a specific cellular distribution between neurons and astrocytes is revealed which suggests that a population of astrocytes is a lactate ‘source’ while neurons may be a lactate ‘sink’. Third, we provide biochemical evidence that lactate is interchangeable with glucose to support oxidative metabolism in cortical neurons. This set of data is consistent with the existence of an activity-dependent astrocyte-neuron lactate shuttle for the supply of energy substrates to neurons.

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...

In view of the neurotrophic effect of vasoactive intestinal peptide (VIP), the regulation of brain-derived neurotrophic factor (BDNF) expression by VIP and the related peptide pituitary adenylate cyclase-activating polypeptide (PACAP) was analysed by Northern blot in primary cultures of cortical neurones. Results reported in this article demonstrate that VIP and PACAP stimulate the expression of BDNF mRNA in primary cultures of cortical neurones and astrocytes. In primary cultures of cortical neurones, induction of BDNF mRNA by VIP and PACAP is completely inhibited by the N-methyl-D-aspartate (NMDA) receptor antagonists MK-801 and AP5, therefore indicating that VIP and PACAP do not stimulate BDNF expression directly but rather by potentiating the effect of glutamate tonically released by neurones and acting at NMDA receptors. In addition to its neurotrophic effects, BDNF has been shown to be involved in neuronal plasticity and results reported here suggest that by stimulating BDNF expression, VIP and PACAP could modulate synaptic plasticity in the cerebral cortex.

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He is grown-up, not young, often bald, strictly male, often a chemist, wearing odd clothes and working on mysterious things, conducting projects which sometimes help save the world, sometimes harm our natural environment. He lives and works - often into the small hours - in a grey laboratory, alone, no colleagues, utterly isolated from the outside world. His 'space' looks like a laboratory equipped with test tubes, with reactive substances but also magic portions; mostly a windowless space, and any windows there are have iron bars. This is how, broadly speaking, and stereotypically, children see scientists. Chemistry and biology are the two most popular branches. Only rarely do we associate these images - which appear to be a simple figment of a child's imagination - to the problem of staff shortages in the 'MINT' sectors in Switzerland and to the shortfall in the number of women scientists. Nonetheless, some of the ideas presented in this article suggest that a child's outlook on science, fairly deep-rooted from as early as 9 or 10 years of age (and surprisingly unchanged by the time these kids reach secondary school) may have an impact on their future career choices. L'ideatorio, at Università della Svizzera italiana, is committed to counteracting this distorted view, in particular by creating particular spaces where children can meet science - not a 'crazy', but a normal and also female, science. In these spaces, chemistry is not synonymous with bad smells and pollution, but with benefits and discovery.