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Dec 07

STEER Researcher Henry Nick studies how sleep fragmentation and loss of orexin can lead to brain inflammation

Posted by Community Engagement Core 
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My name is Henry Nick, and I am a rising junior at Penn. I am majoring in Neuroscience with minors in Chemistry, Sociology, and Cognitive Science. This summer, I was lucky to be matched with Dr. Sigrid Veasey and her lab in the Center for Sleep and Circadian Neurobiology to examine the effects of sleep fragmentation and orexin loss on inflammation of the brain.

What is your summer research project? 

This summer, my primary project sought to explore the effects of sleep fragmentation and loss of orexinergic neurons on the health and wellbeing of the brain. Under guidance and mentorship from Dr. Veasey and the peers and colleagues in her lab, I have been able to analyze hippocampi from multiple groups of mice – rested wild type, sleep fragmented wild type, rested orexin knockout, and sleep fragmented orexin knockout – to determine if sleep fragmentation causes an enhanced proinflammatory response in brains when orexinergic neurons – neurons that determine whether an animal should be asleep or awake – are not active. 

What are the implications of your research? 

Sleep fragmentation occurs when there are frequent, abnormal awakenings during the sleep-wake cycle, disrupting the natural sleep cycle. Artificial lighting, longer work commuting times, night-shift work, and increasing availability of computers and televisions have all contributed to shortened sleep times, and is especially common in more densely populated inner city environments, where all of these are more common. These interruptions cause negative impacts on cognitive performance; including mood, attention, memory, and executive function.

Lack of sleep causes a loss of orexin neurons which causes systemic inflammation in monocytes. Monocytes are a type of white blood cell produced in the bone marrow. They fight infections and remove dead or damaged cells and fight cancer cells. Orexin is a neuropeptide that regulates various physiological phenomena such as wakefulness, feeding, reward, and thermogenesis. The body energy level influences orexin neuronal activity to coordinate arousal and energy homeostasis. Loss of orexin signaling has been linked to narcolepsy, obesity, and age-related disorders caused by reduced energy expenditure, reduced food intake, and weight loss.

What new skills have you gained through your research? 

It was a nice change of pace to be able to conduct in-person research this summer through the STEER program coming out of a long period of remote work. My research relied on examining mouse brains, so I had to go through a rigorous training protocol in order to ensure I was adequately trained to work with animals. This taught me a lot behind the ethics of research which I know will be a lifelong skill. Within the lab, I focused on immunohistochemistry, which provides researchers with a window into inflammation. This staining technique uses antibodies conjugated to enzymes that catalyze reactions to form detectable compounds to visualize and localize specific antigen markers in a tissue sample. I was unfamiliar with this entire process prior to STEER but had to go through it multiple times this summer since I was looking for a whole array of protein markers. I was grateful to have this opportunity to build my wet lab and animal handling skills which I know I will use a lot in the future.

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