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Cross-Species Investigation of Hypersomnia Genetics: A Role for Synaptic Adhesion Molecules Kyla Mace
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Mace, Kyla, author.
- Language:
- English
- Subjects (All):
- Neurosciences.
- Developmental biology.
- Genetics.
- 0317.
- 0758.
- 0369.
- Local Subjects:
- Neurosciences.
- Developmental biology.
- Genetics.
- 0317.
- 0758.
- 0369.
- Physical Description:
- 1 electronic resource (138 pages)
- Contained In:
- Dissertations Abstracts International 86-07B
- Place of Publication:
- Ann Arbor : ProQuest Dissertations and Theses, 2024
- Language Note:
- English
- Summary:
- Idiopathic hypersomnia (IH) is a poorly understood sleep disorder characterized by excessive daytime sleepiness despite normal nighttime sleep. Combining human genomics with behavioral and mechanistic studies in fish and flies, we uncover a role for beat-Ia/CADM2, synaptic adhesion molecules of the immunoglobulin superfamily, in excessive sleepiness. Neuronal knockdown of Drosophila beat-Ia results in sleepy flies and loss of the vertebrate ortholog of beat-Ia, CADM2, results in sleepy fish. We delineate a developmental function for beat-Ia in synaptic elaboration of neuropeptide F (NPF) neurites projecting to the suboesophageal zone (SEZ) of the fly brain. Brain connectome and experimental evidence demonstrate these NPF outputs synapse onto a subpopulation of SEZ GABAergic neurons to stabilize arousal. NPF is the Drosophila homolog of vertebrate neuropeptide Y (NPY), and an NPY receptor agonist restores sleep to normal levels in zebrafish lacking CADM2. These findings point towards NPY modulation as a treatment target for human hypersomnia
- Notes:
- Source: Dissertations Abstracts International, Volume: 86-07, Section: B.
- Advisors: Kayser, Matthew Committee members: Kelz, Max; Sehgal, Amita; Raizen, David
- Ph.D. University of Pennsylvania 2024
- Local Notes:
- School code: 0175
- ISBN:
- 9798302182517
- Access Restriction:
- Restricted for use by site license
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