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Behavioral Disturbances in Estrogen-Related Receptor alpha-Null Mice

Eating disorders, such as anorexia nervosa and bulimia nervosa, are common and severe mental illnesses of unknown etiology. Recently, we identified a rare missense mutation in the transcription factor estrogen-related receptor alpha (ESRRA) that is associated with the development of eating disorders...

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Detalles Bibliográficos
Autores principales: Cui, Huxing, Lu, Yuan, Khan, Michael Z., Anderson, Rachel M., McDaniel, Latisha, Wilson, Hannah E., Yin, Terry C., Radley, Jason J., Pieper, Andrew A., Lutter, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4440329/
https://www.ncbi.nlm.nih.gov/pubmed/25865889
http://dx.doi.org/10.1016/j.celrep.2015.03.032
Descripción
Sumario:Eating disorders, such as anorexia nervosa and bulimia nervosa, are common and severe mental illnesses of unknown etiology. Recently, we identified a rare missense mutation in the transcription factor estrogen-related receptor alpha (ESRRA) that is associated with the development of eating disorders. However, little is known about ESRRA function in the brain. Here, we report that Esrra is expressed in the mouse brain and demonstrate that Esrra levels are regulated by energy reserves. Esrra-null female mice display a reduced operant response to a high-fat diet, compulsivity/behavioral rigidity, and social deficits. Selective Esrra knockdown in the prefrontal and orbitofrontal cortices of adult female mice recapitulates reduced operant response and increased compulsivity, respectively. These results indicate that Esrra deficiency in the mouse brain impairs behavioral responses in multiple functional domains.