Stanford Psychiatry receives grant to study contribution of hypocretin neuron activity to Alzheimer's related sleep disturbances

May 2024

Oscar Gonzalez, PhD

We are thrilled to share that Stanford Psychiatry’s Oscar Gonzalez, postdoctoral scholar of psychiatry and behavioral sciences, has received a grant from the National Institute on Aging entitled “Contribution of hypocretin neuron activity to Alzheimer's related sleep disturbances.”

Sleep is a very well conserved behavioral state across all animals - its precise homeostatic regulation is vital for maintaining good sleep quality and a healthy life. Patients with Alzheimer’s disease show signs of disrupted sleep architecture, characterized by fragmented sleep patterns. Though the exact mechanism underlying fragmented sleep in Alzheimer’s patients remains unknown, it may involve disrupted encoding of homeostatic sleep pressures by wake- promoting hypocretin neurons of the lateral hypothalamus.

This early-career grant builds on recent work that has demonstrated that hyperexcitability of wake-promoting hypocretin neurons of the lateral hypothalamus, resulting from natural aging, may underlie increased sleep fragmentation during aging.

“I will investigate the impact of Alzheimer’s disease-related accumulation of beta-amyloid on hypocretin neuron activity, and subsequent impacts on homeostatic sleep pressure and increased sleep fragmentation,” says Dr. Gonzalez, “with the aim of elucidating the underlying mechanisms driving sleep disturbances in Alzheimer’s disease – a key step in advancing our understanding of Alzheimer’s disease progression and treatment.”

Dr. Gonzalez works with research mentor Luis de Lecea, a professor in the Department of Psychiatry and Behavioral Sciences. The de Lecea Lab studies the role of neuromodulators in mammalian behavior, especially behaviors related to sleep, reward, stress, and learning/memory. In the de Lecea lab, Dr. Gonzalez combines theoretical and experimental techniques to study the impact of sleep pressure on wake-promoting brain regions, its influence on sleep architecture, and disruption in neurodegenerative disorders. Recent publications Dr. Gonzalez has contributed to include “Optogenetic and pharmacological interventions link hypocretin neurons to impulsivity in mice” published in the journal Communications Biology, and “Adolescent sleep defects and dopaminergic hyperactivity in mice with a schizophrenia-linked Shank3 mutation” published in Sleep.

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