Author: Robert Adams
Adams, Robert, 2024 Relationships Between Bioenergetics, Physiological Activity, and Lysosome Function in Human Neurons, Flinders University, College of Medicine and Public Health
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Chapter 1 provides a background overview of neuronal glucose metabolism and energy expenditures, and links the disruption of impaired neuronal bioenergetics to disease pathology. In particular, calcium mediated excitotoxicity, proteolytic dysfunction, and α-synucleinopathy in relation to the neurodegenerative disorder Parkinson’s Disease are briefly discussed regarding how they may be initiated or intensified as a consequence of bioenergetic stress.
In Chapter 2, I discuss the results of experiments using human midbrain neuronal cultures that query whether modulation of neuronal electrophysiological activity can raise energy levels and restore function to an impaired lysosomal system.
Chapter 3 explores how insufficient glucose metabolism, induced via extracellular hypoglycemia, impacts the development of highly synchronised burst spiking activity in human midbrain neuronal cultures. Our results illuminate how glucose hypometabolism may impair dendritic networks and neurotransmission.
In Chapter 4, the effects of mitochondrial dysfunction, induced with mitochondrial toxins, upon the electrophysiological function of human midbrain neuronal cultures are examined. The results of preliminary experiments are compared to similar work published by Elzoheiry et al. (2019); discrepancies between observations raise questions regarding the differential effects of metabolic and oxidative stress upon neuronal synchronous activity.
Chapter 5 switches from human neuronal cultures to rat primary cultures. In this chapter, BrainPhys (a medium designed to provide a physiological environment for human neuronal cultures) is optimised for rat primary cortical neuronal culture and is demonstrated to out-perform Neurobasal (a widely used and popular medium for rodent neuronal culture) regarding the long-term maintenance of rat primary cortical neurons.
Chapter 6 investigates phenotypic differences between induced pluripotent stem cell derived neuronal cultures generated from healthy donors and donors with mucopolysaccharidosis type III A – a lysosomal storage disorder. Here, we characterise pathological differences in the lysosomal compartment of MPS IIIA neuronal cultures.
Keywords: neuron, ipsc, stem cell, parkinson's, bioenergetics, hypoglycemia, lysosome, electrophysiology
Subject: Neuroscience thesis
Thesis type: Doctor of Philosophy
Completed: 2024
School: College of Medicine and Public Health
Supervisor: Cedric Bardy