Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10215523 | Neurobiology of Disease | 2019 | 26 Pages |
Abstract
Prader-Willi and the related Schaaf-Yang Syndromes (PWS/SYS) are rare neurodevelopmental disorders characterized by overlapping phenotypes of high incidence of autism spectrum disorders (ASD) and neonatal feeding difficulties. Based on clinical and basic studies, oxytocin pathway defects are suggested to contribute disease pathogenesis but the mechanism has been poorly understood. Specifically, whether the impairment in oxytocin system is limited to neuropeptide levels and how the functional properties of broader oxytocin neuron circuits affected in PWS/SYS have not been addressed. Using cell type specific electrophysiology, we investigated basic synaptic and cell autonomous properties of oxytocin neurons in the absence of MAGEL2; a hypothalamus enriched ubiquitin ligase regulator that is inactivated in both syndromes. We observed significant suppression of overall ex vivo oxytocin neuron activity, which was largely contributed by altered synaptic input profile; with reduced excitatory and increased inhibitory currents. Our results suggest that dysregulation of oxytocin system goes beyond altered neuropeptide expression and synaptic excitation inhibition imbalance impairs overall oxytocin pathway function.
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Authors
Tayfun Ates, Merve Oncul, Pelin Dilsiz, Iskalen Cansu Topcu, Cihan Civan Civas, Muhammed Ikbal Alp, Iltan Aklan, Edanur Ates Oz, Yavuz Yavuz, Bayram Yilmaz, Nilufer Sayar Atasoy, Deniz Atasoy,