Metabolism of oligodendrocytes and its involvement in axo‐glia interaction

Trevisiol, Andrea

dc.contributor.advisor	Nave, Klaus-Armin Prof. Dr.
dc.contributor.author	Trevisiol, Andrea
dc.date.accessioned	2019-03-12T12:00:27Z
dc.date.available	2019-03-12T12:00:27Z
dc.date.issued	2019-03-12
dc.identifier.uri	http://hdl.handle.net/11858/00-1735-0000-002E-E5C4-3
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-7324
dc.language.iso	eng	de
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ddc	570	de
dc.title	Metabolism of oligodendrocytes and its involvement in axo‐glia interaction	de
dc.type	doctoralThesis	de
dc.contributor.referee	Rizzoli, Silvio Prof. Dr.
dc.date.examination	2018-02-26
dc.description.abstracteng	In white matter, axonal energy homeostasis critically depends on glial support. Failure in glial-mediated delivery of metabolic substrates into the axonal compartment results in axonal energy deficit and may anticipate axonal degeneration observed in myelin disorders and several neurodegenerative diseases. In mice, transgenic expression of an ATP-sensor in neurons allowed us to visualize axonal energy content in acutely isolated optic nerves while simultaneously performing electrophysiological compound action potentials (CAP) recordings. The real-time monitoring of activity-dependent axonal ATP revealed a strong correlation between axonal energy fluctuations and nerve conduction. Importantly, upon pharmacological inhibition of endogenous lactate metabolism while under continuous glucose supply, ATP-CAP correlation was disrupted, suggesting that the axonal glycolysis products alone were insufficient to maintain axonal mitochondrial energy metabolism during spiking activity. To determine possible metabolic consequences of myelin defects we monitored ATP and CAP in Plp1-null optic nerves. Genetic ablation of Plp1, encoding a myelin membrane protein, serves as a model of spastic paraplegia type-2, where functional but structurally destabilized myelin sheaths lead to secondary axonal loss. We found that the energy metabolism of myelinated axons of Plp1-null optic nerves is perturbed long before the onset of clinical symptoms and major pathological changes. These observations motivated us to assess the metabolic properties of spinal cord fibres in vivo to allow long-term studies involving demyelination and remyelination models. The parallel monitoring of axonal ATP and CAP is a powerful tool to study white matter metabolism and metabolic support mechanisms under physiological conditions and in models of neurodegenerative disorders.	de
dc.contributor.coReferee	Hülsmann, Swen Prof. Dr.
dc.subject.eng	White matter	de
dc.subject.eng	ATP	de
dc.subject.eng	axo-glia	de
dc.subject.eng	metabolism	de
dc.subject.eng	cAP	de
dc.subject.eng	optic nerve	de
dc.subject.eng	PLP1	de
dc.identifier.urn	urn:nbn:de:gbv:7-11858/00-1735-0000-002E-E5C4-3-8
dc.affiliation.institute	Göttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB)	de
dc.subject.gokfull	Biologie (PPN619462639)	de
dc.identifier.ppn	1673693237

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GGNB - Göttinger Graduiertenzentrum für Neurowissenschaften, Biophysik und molekulare Biowissenschaften [1114]
GGNB - Göttingen Graduate Center for Neurosciences, Biophysics and Molecular Biosciences

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