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2022-02-01

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cc-by-nc-nd (c) Elsevier, 2021
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/183707

Hypothalamic pregnenolone mediates recognition memory in the context of metabolic disorders

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Recurs relacionat

https://doi.org/10.1016/j.cmet.2021.12.023

Resum

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.

Matèries

Trastorns del metabolisme, Hipotàlem, Trastorns de la memòria

Matèries (anglès)

Disorders of metabolism, Hypothalamus, Memory disorders

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Articles publicats en revistes (Biomedicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Institut de Neurociències (UBNeuro))

Citació

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 PINEDA, Amanda, FERNÁNDEZ-CHECA TORRES, José carlos, CLARET I CARLES, Marc. Hypothalamic pregnenolone mediates recognition memory in the context of metabolic disorders. _Cell Metabolism_. 2021. Vol. 34, núm. 2, pàgs. 269-284. [consulta: 21 de gener de 2026]. ISSN: 1550-4131. [Disponible a: https://hdl.handle.net/2445/183707]

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