Computational Modeling of Plasticity and Metabolism in Neurons and Skeletal Muscle PDF Download

Author: Allen Leung
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Languages : en
Pages : 0

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Book Description
Biological processes resulting in observable cell state changes, such as synaptic plasticity inneuronal dendritic spines and muscular hypertrophy in skeletal muscles, share common characteristics. Both are influenced by calcium signaling, metabolic networks, mitochondria, and protein kinase activation. This research presents computational models of these processes, offering insights into synaptic plasticity and the skeletal muscle response to exercise. The first model is a spatial representation of mitochondrial ATP generation during calcium signaling in neurons, emphasizing the role of mitochondrial ER contact sites in increasing calcium levels in the mitochondria, thus enhancing mitochondrial potential. This model underscores the importance of subcellular geometry, metabolic consumption rates, and transport processes in ATP production, in addition to enzymatic activity. The second model is a compartmental model exploring the role of signaling frequency in protein kinase activation in dendritic spines. This model analyzes the interaction between the canonical neuronal signaling cascade, the AMP-Activated Protein Kinase (AMPK) cascade, and the insulin signaling cascade in conditions of high neurotransmitter stimulation rates, which activate calcium signaling and consume significant cellular energy. The final model, a logic-based representation of skeletal muscle signaling in response to resistance, endurance, and sprint exercise, investigates potential mechanisms of exercise-induced changes in mitochondrial morphology. Together, these models deepen our understanding of the dynamic interplay between signaling and metabolism in synaptic plasticity and exercise physiology, laying the groundwork for further investigation and potential development of therapeutic strategies for neurological disorders and improvements in exercise efficiency.