Yufan Zhang

The Impact of Mitochondrial Dysregulation in LC-NE Neurons on Sleep

Mitochondrial dysregulation has emerged as a cause for certain forms of Parkinson’s disease. Investigations of the mechanisms linking mitochondrial function to Parkinson’s have focused on the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc-DA neurons). Norepinephrine-releasing neurons in the locus coeruleus (LC-NE neurons) rely on mitochondria for their daily activity in healthy individuals and also severely degenerate in Parkinson’s. Both SNc-DA neurons and LC-NE neurons are crucial for maintaining various aspects of wakefulness, but it is unclear whether mitochondrial dysregulation in each neuron population distinctly impacts sleep disturbances characteristic of Parkinson’s. For my project, I will address the hypothesis that mitochondrial dysregulation in LC-NE neurons versus that in SNc-DA neurons will have different effects on sleep in a mouse model, which could provide insight for targeted therapies to improve sleep in patients. Toward this goal, I will study mice using a targeted genetic approach where a key mitochondrial transcription factor, Tfam, would be knocked out in either SNc-DA or LC-NE neurons using the Cre-Lox recombination system and compare 24-hour sleep recording data generated from electroencephalography/electromyography.

Message to Sponsor

Thank you so much for giving me the opportunity and resources to carry out my project. I hope this research will provide experimental support for the etiological role of mitochondrial disruption in LC in sleep disturbances observed in PD patients. I'm incredibly excited to dive into this project with my mentor, and I deeply appreciate your kindness and generosity.
  • Major: MCB-Neurobiology
  • Sponsor: Leadership Fund
  • Mentor: Yang Dan