Lactate and Ketone Bodies Act as Energy Substrates as Well as Signal Molecules in the Brain

Astroglia or astrocytes, the most abundant cells in the brain, are interposed between neuronal synapses and the microvasculature in the brain’s gray matter. This unique anatomical location allows astroglia to play pivotal roles in brain metabolism as well as in the regulation of cerebral blood flow. In particular, astroglial cellular metabolic compartmentation exerts supportive roles in dedicating neurons to the generation of action potentials and protects neurons against the oxidative stress associated with their high energy consumption. Key products of astroglia include lactate and ketone bodies (beta-hydroxybutyrate and acetoacetate), which can also be produced avidly by muscle and liver, respectively. Therefore, brain cells, skeletal muscles, and hepatocytes constitute a metabolic compartmentation in the whole body. In this chapter, I will focus on brain cells, especially astroglia, since the impairment of normal astroglial function can lead to numerous neurological disorders including stroke, neurodegenerative diseases, and neuro-immunological diseases. I will also discuss the metabolic responses of brain cells in terms of food consumption and exercise. A better understanding of the astroglial metabolic response is expected to lead to the development of novel therapeutic strategies for diverse neurological diseases.

Subcellular Compartments Interplay for Carbon and Nitrogen Allocation in Chromera velia and Vitrella brassicaformis

Endosymbioses necessitate functional cooperation of cellular compartments to avoid pathway redundancy and streamline the control of biological processes. To gain insight into the metabolic compartmentation in chromerids, phototrophic relatives to apicomplexan parasites, we prepared a reference set of proteins probably localized to mitochondria, cytosol, and the plastid, taking advantage of available genomic and transcriptomic data. Training of prediction algorithms with the reference set now allows a genome-wide analysis of protein localization in Chromera velia and Vitrella brassicaformis. We confirm that the chromerid plastids house enzymatic pathways needed for their maintenance and photosynthetic activity, but for carbon and nitrogen allocation, metabolite exchange is necessary with the cytosol and mitochondria. This indeed suggests that the regulatory mechanisms operate in the cytosol to control carbon metabolism based on the availability of both light and nutrients. We discuss that this arrangement is largely shared with apicomplexans and dinoflagellates, possibly stemming from a common ancestral metabolic architecture, and supports the mixotrophy of the chromerid algae.

Subcellular compartments interplay for carbon and nitrogen allocation in Chromera velia and Vitrella brassicaformis

ABSTRACTEndosymbioses necessitate functional cooperation of cellular compartments to avoid pathway redundancy and streamline the control of biological processes. To gain insight into the metabolic compartmentation in chromerids, phototrophic relatives to apicomplexan parasites, we prepared a reference set of proteins probably localized to mitochondria, cytosol and the plastid, taking advantage of available genomic and transcriptomic data. Training of prediction algorithms with the reference set now allows a genome-wide analysis of protein localization in C. velia and V. brassicaformis. We confirm that the chromerid plastids house enzymatic pathways needed for their maintenance and photosynthetic activity, but for carbon and nitrogen allocation, metabolite exchange is necessary with the cytosol and mitochondria. This indeed suggests that the regulatory mechanisms operate in the cytosol to control carbon metabolism based on the availability of both light and nutrients. We discuss that this arrangement is largely shared with apicomplexans and dinoflagellates, possibly stemming from a common ancestral metabolic architecture, and supports the mixotrophy of the chromerid algae.

Compartmentalised energy metabolism supporting glutamatergic neurotransmission in response to increased activity in the rat cerebral cortex: A 13C MRS study in vivo at 14.1 T

Many tissues exhibit metabolic compartmentation. In the brain, while there is no doubt on the importance of functional compartmentation between neurons and glial cells, there is still debate on the specific regulation of pathways of energy metabolism at different activity levels. Using 13C magnetic resonance spectroscopy (MRS) in vivo, we determined fluxes of energy metabolism in the rat cortex under α-chloralose anaesthesia at rest and during electrical stimulation of the paws. Compared to resting metabolism, the stimulated rat cortex exhibited increased glutamate–glutamine cycle (+67 nmol/g/min, +95%, P < 0.001) and tricarboxylic (TCA) cycle rate in both neurons (+62 nmol/g/min, +12%, P < 0.001) and astrocytes (+68 nmol/g/min, +22%, P = 0.072). A minor, non-significant modification of the flux through pyruvate carboxylase was observed during stimulation (+5 nmol/g/min, +8%). Altogether, this increase in metabolism amounted to a 15% (67 nmol/g/min, P < 0.001) increase in CMRglc(ox), i.e. the oxidative fraction of the cerebral metabolic rate of glucose. In conclusion, stimulation of the glutamate–glutamine cycle under α-chloralose anaesthesia is associated to similar enhancement of neuronal and glial oxidative metabolism.