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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
Trastorns de la memòria
Disorders of metabolism
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:
It is part of: Cell Metabolism, 2021, vol. 34, num. 2, p. 269-284
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ISSN: 1550-4131
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Biomedicina)
Articles publicats en revistes (Institut de Neurociències (UBNeuro))

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