Henriques 2013 Thesis Universidade de Coimbra - Portugal

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Henriques TAF (2013) High-resolution respirometry for metabolic profiling of acute rat hippocampal slices. Thesis Universidade de Coimbra - Portugal 38pp.

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Henriques TAF (2013) Thesis Universidade de Coimbra - Portugal

Abstract: There are still many unanswered questions in the field of brain bioenergetics and the question of which substrates normally fuel brain metabolism remains unresolved. In particular, it is not clear whether substrate preference is different between neurons and astrocytes, if this preference changes during increased neuronal activity or if the primary pathway to metabolize said substrate is aerobic glycolysis or the tricarbocylic acid (TCA) cycle. Here we attempt to offer some insight on this problematic by performing highresolution respirometry on acute hippocampal slices to evaluate tissue bioenergetics under different metabolic states. By using intact hippocampal slices, the intricate cellular interactions between neurons and astrocytes are maintained, as well as the neuronal circuitry, aspects that certainly have a critical role in the regulation of such metabolic pathways and crosstalks. We show that activation of hippocampal slices by exogenous glutamate leads to an increase in oxidative metabolism, suggesting higher TCA cycle activity and little to no contribution of aerobic glycolysis. We also show that both basal and activity-induced increase of respiration in hippocampal slices can be fuelled by lactate. These results suggest that hippocampal cells readily use lactate as a substrate of oxidative metabolism and that even in the situation of increased neuronal activity, lactate is a good alternative to glucose. As predicted, •NO titration decreased oxygen consumption rate (OCR) in acute rat hippocampal slices. This effect of nitric oxide on mitochondrial respiration has been showed in isolated mitochondria, synaptosomes and intact cells, but not in rat hippocampal slices, a model that maintains the neural cytoarchitecture and the functional cellular relationship between neurons and astrocytes.

Keywords: Respirometria de alta defenição, Hipocampo, Fatias Óxido, Nítrico Neurometabolismo

Labels: MiParea: Respiration, Comparative MiP;environmental MiP 

Organism: Rat  Tissue;cell: Nervous system  Preparation: Intact cells 

Coupling state: LEAK, ROUTINE, ET  Pathway: N, S, ROX  HRR: Oxygraph-2k