The Glyoxalase 1 – Methylglyoxal Pathway Regulates Neurite Development of Cerebral Cortical Neurons in the Mammalian Brain
Date
2020-05
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Abstract
Newborn neurons of the mammalian cerebral cortex undergo substantial morphological changes during development. Neurite elongation and branching are crucial morphological changes in early neuronal development that are necessary for the formation of dendrites and axons – structural elements that allow neurons to communicate with each other and form circuits. One factor that has received little attention as a possible regulator of neurite development is metabolism. In this thesis, I show that methylglyoxal, an intermediate metabolite of glycolysis, and its metabolizing enzyme, glyoxalase 1 (Glo1) regulate the elongation and branching of neurites. Knockdown of Glo1 expression using short-hairpin RNA or inhibiting the enzymatic activity of Glo1 in cultured mouse cortical neurons reduces neurite length and impairs branching organization. Furthermore, I found that knockdown or inhibition of Glo1 activity perturbs development of both excitatory projection neurons and inhibitory interneurons. When neurons are treated with excessive methylglyoxal, morphological perturbation is recapitulated. These results suggest a link between methylglyoxal metabolism and neuronal development and provide the foundation for future studies of the molecular mechanisms that mediate this metabolic regulation.
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Keywords
Neurite development, neurite branching, metabolism, glyoxalase 1, methylglyoxal, excitatory projection neurons
Citation
Mohammad, L. (2020). The Glyoxalase 1 – Methylglyoxal pathway regulates neurite development of cerebral cortical neurons in the mammalian brain (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.