Investigating the molecular pathway through which L-Lactate interacts with synaptic NMDAR to modulate neuronal plasticity

Handle URI:
http://hdl.handle.net/10754/621939
Title:
Investigating the molecular pathway through which L-Lactate interacts with synaptic NMDAR to modulate neuronal plasticity
Authors:
Ibrahim, Engy ( 0000-0003-1534-452X )
Abstract:
In the brain, glycogen, the storage form of glucose, is exclusively localized in astrocytes (Magistretti and Allaman, 2015). Glycogenolysis leads to the production of L-lactate, which is shuttled to neurons for ATP production. Interestingly, L-lactate was recently shown to be not only a source of energy, but also a signaling molecule to neurons. This was demonstrated through the inhibition of L-lactate production or transport in an inhibitory avoidance paradigm, where the rodents developed amnesia. This inhibition of memory consolidation was rescued by L-lactate and not by equicaloric glucose emphasizing that L-lactate acts as a signaling molecule as well (Suzuki et al., 2011). A recent study in our laboratory suggests that the action of L-lactate takes place through a cascade of molecular events via the modulation of N-methyl-D-aspartate receptor (NMDAR) activity (Yang et al., 2014). Since NADH produced similar results to those seen with L-lactate, it was hypothesized that the action of the latter is based on altering the redox state of the cell, in particular in view of the fact that redox-sensitive sites are present on the NMDAR. However, the precise molecular mechanism underlying the apparent change in the NMDAR activity is not fully elucidated. The objective of this study is to explore those mechanisms.
Advisors:
Magistretti, Pierre J. ( 0000-0002-6678-320X )
Committee Member:
Merzaban, Jasmeen ( 0000-0002-7276-2907 ) ; Aranda, Manuel ( 0000-0001-6673-016X ) ; Chatton, Jean-Yves
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division
Program:
Bioscience
Issue Date:
Dec-2016
Type:
Dissertation
Appears in Collections:
Dissertations

Full metadata record

DC FieldValue Language
dc.contributor.advisorMagistretti, Pierre J.en
dc.contributor.authorIbrahim, Engyen
dc.date.accessioned2016-12-05T09:50:26Z-
dc.date.available2016-12-05T09:50:26Z-
dc.date.issued2016-12-
dc.identifier.urihttp://hdl.handle.net/10754/621939-
dc.description.abstractIn the brain, glycogen, the storage form of glucose, is exclusively localized in astrocytes (Magistretti and Allaman, 2015). Glycogenolysis leads to the production of L-lactate, which is shuttled to neurons for ATP production. Interestingly, L-lactate was recently shown to be not only a source of energy, but also a signaling molecule to neurons. This was demonstrated through the inhibition of L-lactate production or transport in an inhibitory avoidance paradigm, where the rodents developed amnesia. This inhibition of memory consolidation was rescued by L-lactate and not by equicaloric glucose emphasizing that L-lactate acts as a signaling molecule as well (Suzuki et al., 2011). A recent study in our laboratory suggests that the action of L-lactate takes place through a cascade of molecular events via the modulation of N-methyl-D-aspartate receptor (NMDAR) activity (Yang et al., 2014). Since NADH produced similar results to those seen with L-lactate, it was hypothesized that the action of the latter is based on altering the redox state of the cell, in particular in view of the fact that redox-sensitive sites are present on the NMDAR. However, the precise molecular mechanism underlying the apparent change in the NMDAR activity is not fully elucidated. The objective of this study is to explore those mechanisms.en
dc.language.isoenen
dc.subjectLactateen
dc.subjectCalcium imagingen
dc.subjectmemoryen
dc.subjectNMDARen
dc.titleInvestigating the molecular pathway through which L-Lactate interacts with synaptic NMDAR to modulate neuronal plasticityen
dc.typeDissertationen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
thesis.degree.grantorKing Abdullah University of Science and Technologyen_GB
dc.contributor.committeememberMerzaban, Jasmeenen
dc.contributor.committeememberAranda, Manuelen
dc.contributor.committeememberChatton, Jean-Yvesen
thesis.degree.disciplineBioscienceen
thesis.degree.nameDoctor of Philosophyen
dc.person.id113373en
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