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https://hdl.handle.net/2445/183707
Title: | Hypothalamic pregnenolone mediates recognition memory in the context of metabolic disorders |
Author: | Ramírez, Sara Haddad Tovolli, Roberta Radosevic, Marija Toledo Soler, Miriam Pané, Adriana Alcolea, Daniel Ribas, Vicent Pozo, Macarena Obri, Arnaud Milà Guasch, Maria Eyre, Elena Gómez Valadés, Alicia G. Chivite, Iñigo Van Eeckhout, Tomas Zalachoras, Ioannis Altirriba Gutiérrez, Jordi Bauder, Corinna Imbernón, Mónica Garrabou Tornos, Glòria García Ruiz, Carmen Nogueiras, Rubén Soto del Cerro, David Gasull Casanova, Xavier Sandi, Carmen Brüning, Jens C. Fortea Ormaechea, Juan Jiménez, Amanda Fernández-Checa Torres, José Carlos Claret i Carles, Marc |
Keywords: | Trastorns del metabolisme Hipotàlem Trastorns de la memòria Disorders of metabolism Hypothalamus Memory disorders |
Issue Date: | 1-Feb-2022 |
Publisher: | Cell Press |
Abstract: | Obesity and type-2 diabetes are associated with cognitive dysfunction. Since the hypothalamus is implicated in energy balance control and memory disorders, we hypothesized that specific neurons in this brain region are at the interface of metabolism and cognition. Acute obesogenic diet administration in mice impaired recognition memory due to defective production of the neurosteroid-precursor pregnenolone in the hypothalamus. Genetic interference with pregnenolone synthesis by Star deletion in hypothalamic POMC, but not AgRP neurons, deteriorated recognition memory independently of metabolic disturbances. Our data suggested that pregnenolone's effects on cognitive function were mediated via an autocrine mechanism on POMC neurons, influencing hippocampal long-term potentiation. The relevance of central pregnenolone on cognition was also confirmed in metabolically-unhealthy obese patients. Our data reveals an unsuspected role for POMC neuron-derived neurosteroids in cognition. These results provide the basis for a framework to investigate new facets of POMC neuron biology with implications for cognitive disorders. |
Note: | Versió postprint del document publicat a: https://doi.org/10.1016/j.cmet.2021.12.023 |
It is part of: | Cell Metabolism, 2021, vol. 34, num. 2, p. 269-284 |
URI: | https://hdl.handle.net/2445/183707 |
Related resource: | https://doi.org/10.1016/j.cmet.2021.12.023 |
ISSN: | 1550-4131 |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Institut de Neurociències (UBNeuro)) Articles publicats en revistes (Biomedicina) |
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