Exploring the Neurochemistry Behind Parkinson’s-related Sleep Disruption
The primary impact of Parkinson’s disease (PD) is a progressive loss of neurons in the brain that produce dopamine. Dopamine is a small signaling molecule used by neurons to relay messages and commands important for many tasks, including coordinated movement. As dopamine levels decline over time, the ability to perform these tasks decreases and manifests as PD symptoms.
It was recently discovered that dopamine likely plays a critical role in regulating sleep. People with PD often experience disrupted sleep as an early symptom of the disease, which significantly impairs health even before movement symptoms begin. Xiaolin (Lindsay) Huang, PhD, a recipient of a Parkinson’s Foundation Postdoctoral Fellowship, is exploring the neurochemistry behind dopamine and sleep, generating new knowledge to guide future therapies that treat PD-associated sleep disruption.
Research suggests that dopamine is important for waking up and staying awake. However, diminishing dopamine in PD does not lead to chronic sleepiness like this finding would suggest. Dr. Huang, under the mentorship of Yang Dan, PhD, at the University of California, Berkeley, is solving this puzzle by investigating how dopamine signaling coordinates with the “sleep pressure” molecule called adenosine, as well as how dopamine deficits affect a sleep-regulating region of the brain called the medialsubstantia nigra pars reticulata (mSNr).
“By uncovering the neural mechanisms driving PD-associated sleep disturbances, the study will shed light on a critical and underexplored aspect of the disease.” - Dr. Huang
While dopamine promotes wakefulness, adenosine promotes sleepiness. Adenosine accumulates in the brain throughout the day and eventually overwhelms dopamine levels, leading to growing tiredness until it is time for bed. Using mice with and without simulated PD, Dr. Huang will utilize highly sensitive brain monitoring techniques to observe how PD affects the balance between dopamine and adenosine and how that disruption may impact sleep behaviors.
Additionally, previous research from Dr. Dan’s lab has revealed that the mSNr region of the brain is important for regulating sleep-wake behaviors. Using the same experimental PD mice, Dr. Huang will assess if and how dopamine loss impairs neuron activity in the mSNr region, further disrupting sleep patterns in those animals.
Altogether, these investigations into how PD-related sleep disruption are related to adenosine levels and mSNr changes can lead to future research and treatment development addressing this debilitating non-movement PD symptom. When asked what this award means for her work and career in PD research, Dr. Huang said “Receiving the Parkinson’s Foundation Postdoctoral Fellowship is both an honor and a pivotal step in my scientific journey. Ultimately, the findings may inform the development of new therapies to improve sleep and enhance quality of life for people living with PD.”
