Plasticity-dependent modulation of mitochondrial biogenesis determining motor neuron function and vulnerability

by Camille Lancelin
Doctoral thesis
Date of Examination:2015-09-29
Date of issue:2016-10-10
Advisor:Dr. Till Marquardt
Referee:Prof. Dr. Nils Brose
Referee:Dr. Judith Stegmüller
Persistent Address: http://dx.doi.org/10.53846/goediss-5873

 

 

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Abstract

English

Axon terminals are likely the compartments of highest energy demand in the particularly active and polarized cells that are motor neurons. Paradoxically, although the particularly high-energy demand of motor neurons could make them more prone to energetic stress, endurance exercise appears to mediate the strengthening of the neuromuscular synapse. Moreover, tight regulation of mitochondrial biogenesis is of utmost importance for meeting elevated energy demands in neurons, and thus mitochondrial plasticity may adapt pre-synaptic motor neuron metabolic properties to increased energetic stress. While mitochondrial biogenesis and function have been extensively studied in muscle, much less is known regarding mitochondrial network remodeling at the neuromuscular junction upon exercise. In this study, exercise- induced changes at the neuromuscular junction were directly observed and measured using mice expressing genetically tagged mitochondria specifically in motor neurons, followed by 3D-reconstruction of synaptic structures. In addition, RNA sequencing of muscle as well as dorsal and ventral spinal cord samples from both control and long-term voluntary trained mice, enabled the identification of genes which expression was regulated upon physical activity. Thus, the present study provides insights on the regulations in gene expression that may modulate mitochondrial biogenesis and stress pathways upon physical exercise and how these changes may impact motor neuron function and ultimately mediate exercise beneficial effects.
Keywords: motor neuron; mitochondria; plasticity
 
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