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

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    Engy Ibrahim Dissertation.pdf
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    2.606Mb
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    PDF
    Description:
    Engy Ibrahim Dissertation
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    Type
    Dissertation
    Authors
    Ibrahim, Engy cc
    Advisors
    Magistretti, Pierre J. cc
    Committee members
    Merzaban, Jasmeen cc
    Aranda, Manuel cc
    Chatton, Jean-Yves
    Program
    Bioscience
    KAUST Department
    Biological and Environmental Science and Engineering (BESE) Division
    Date
    2016-12
    Permanent link to this record
    http://hdl.handle.net/10754/621939
    
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    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.
    Citation
    Ibrahim, E. (2016). Investigating the molecular pathway through which L-Lactate interacts with synaptic NMDAR to modulate neuronal plasticity. KAUST Research Repository. https://doi.org/10.25781/KAUST-LGR2H
    DOI
    10.25781/KAUST-LGR2H
    ae974a485f413a2113503eed53cd6c53
    10.25781/KAUST-LGR2H
    Scopus Count
    Collections
    Biological and Environmental Science and Engineering (BESE) Division; Bioscience Program; PhD Dissertations

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