1. Loss of Snord116 impacts lateral hypothalamus, sleep, and food-related behaviors.
- Author
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Pace M, Falappa M, Freschi A, Balzani E, Berteotti C, Lo Martire V, Kaveh F, Hovig E, Zoccoli G, Amici R, Cerri M, Urbanucci A, and Tucci V
- Subjects
- Animals, Disease Models, Animal, Feeding Behavior, Hypothalamic Area, Lateral physiopathology, Hypothalamic Hormones metabolism, Melanins metabolism, Mice, Neurons metabolism, Pituitary Hormones metabolism, Prader-Willi Syndrome metabolism, Prader-Willi Syndrome physiopathology, Behavior, Animal physiology, Hypothalamic Area, Lateral metabolism, Hypothalamus metabolism, Orexins metabolism, RNA, Small Nucleolar genetics, Sleep physiology
- Abstract
Imprinted genes are highly expressed in the hypothalamus; however, whether specific imprinted genes affect hypothalamic neuromodulators and their functions is unknown. It has been suggested that Prader-Willi syndrome (PWS), a neurodevelopmental disorder caused by lack of paternal expression at chromosome 15q11-q13, is characterized by hypothalamic insufficiency. Here, we investigate the role of the paternally expressed Snord116 gene within the context of sleep and metabolic abnormalities of PWS, and we report a significant role of this imprinted gene in the function and organization of the 2 main neuromodulatory systems of the lateral hypothalamus (LH) - namely, the orexin (OX) and melanin concentrating hormone (MCH) - systems. We observed that the dynamics between neuronal discharge in the LH and the sleep-wake states of mice with paternal deletion of Snord116 (PWScrm+/p-) are compromised. This abnormal state-dependent neuronal activity is paralleled by a significant reduction in OX neurons in the LH of mutant mice. Therefore, we propose that an imbalance between OX- and MCH-expressing neurons in the LH of mutant mice reflects a series of deficits manifested in the PWS, such as dysregulation of rapid eye movement (REM) sleep, food intake, and temperature control.
- Published
- 2020
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