dc.contributor.author |
Ramírez, Sara |
dc.contributor.author |
Haddad-Tóvolli, Roberta |
dc.contributor.author |
Radosevic, Marija |
dc.contributor.author |
Toledo, Miriam |
dc.contributor.author |
Pané, Adriana |
dc.contributor.author |
Alcolea, Daniel |
dc.contributor.author |
Ribas, Vicent |
dc.contributor.author |
Milà-Guasch, Maria |
dc.contributor.author |
Pozo, Macarena |
dc.contributor.author |
Obri, Arnaud |
dc.contributor.author |
Eyre Sánchez, Elena |
dc.contributor.author |
Gómez-Valadés, Alicia G. |
dc.contributor.author |
Chivite, Iñigo |
dc.contributor.author |
Van Eeckhout, Tomas |
dc.contributor.author |
Zalachoras, Ioannis |
dc.contributor.author |
Altirriba, Jordi |
dc.contributor.author |
Bauder, Corinna |
dc.contributor.author |
Imbernón, Mónica |
dc.contributor.author |
Garrabou, Gloria |
dc.contributor.author |
Garcia-Ruiz, Carmen |
dc.contributor.author |
Nogueiras, Rubén |
dc.contributor.author |
Soto, David |
dc.contributor.author |
Gasull, Xavier |
dc.contributor.author |
Sandi, Carmen |
dc.contributor.author |
Brüning, Jens C. |
dc.contributor.author |
Fortea, Juan |
dc.contributor.author |
Jiménez, Amanda |
dc.contributor.author |
Fernández-Checa, José C. |
dc.contributor.author |
Claret, Marc |
dc.contributor.author |
Universitat Autònoma de Barcelona |
dc.date |
2022 |
dc.identifier |
https://ddd.uab.cat/record/254984 |
dc.identifier |
urn:10.1016/j.cmet.2021.12.023 |
dc.identifier |
urn:oai:ddd.uab.cat:254984 |
dc.identifier |
urn:pmcid:PMC8815774 |
dc.identifier |
urn:pmc-uid:8815774 |
dc.identifier |
urn:pmid:35108514 |
dc.identifier |
urn:oai:pubmedcentral.nih.gov:8815774 |
dc.identifier |
urn:articleid:19327420v34p269 |
dc.format |
application/pdf |
dc.language |
eng |
dc.publisher |
|
dc.relation |
Fundació la Marató de TV3 20141210 |
dc.relation |
Fundació la Marató de TV3 201614.31 |
dc.relation |
Fundació la Marató de TV3 201916/31 |
dc.relation |
Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-737 |
dc.relation |
Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-1112 |
dc.relation |
Agència de Gestió d'Ajuts Universitaris i de Recerca SLT006/17/00119 |
dc.relation |
Agència de Gestió d'Ajuts Universitaris i de Recerca SLT006/17/125 |
dc.relation |
Agència de Gestió d'Ajuts Universitaris i de Recerca SLT008/18/00127 |
dc.relation |
Agencia Estatal de Investigación PID2019-111669RB-I00 |
dc.relation |
Agencia Estatal de Investigación PID2020-115055RB-I00 |
dc.relation |
European Commission. Horizon 2020 725004 |
dc.relation |
European Commission. Horizon 2020 891247 |
dc.relation |
Instituto de Salud Carlos III PI17/00296 |
dc.relation |
Instituto de Salud Carlos III PI14/01126 |
dc.relation |
Instituto de Salud Carlos III PI17/01019 |
dc.relation |
Instituto de Salud Carlos III PI17/00279 |
dc.relation |
Instituto de Salud Carlos III PI20/0042 |
dc.relation |
Instituto de Salud Carlos III PI16/00963 |
dc.relation |
Instituto de Salud Carlos III INT19/00016 |
dc.relation |
Instituto de Salud Carlos III CP19/00083 |
dc.relation |
Ministerio de Ciencia e Innovación BFU2017-83317-P |
dc.relation |
Ministerio de Ciencia e Innovación FJCI-2016-28911 |
dc.relation |
Ministerio de Ciencia e Innovación IJC2018-037341-I |
dc.relation |
Ministerio de Economía, Industria y Competitividad MDM-2017-0729 |
dc.relation |
Cell Metabolism ; Vol. 34 (february 2022), p. 269-284.e9 |
dc.rights |
open access |
dc.rights |
Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades. |
dc.rights |
https://creativecommons.org/licenses/by-nc-nd/4.0/ |
dc.subject |
Hypothalamus |
dc.subject |
Obesity |
dc.subject |
Diabetes |
dc.subject |
Cognitive function |
dc.subject |
Recognition memory |
dc.subject |
Neurosteroids |
dc.subject |
POMC neurons |
dc.subject |
Pregnenolone |
dc.subject |
Stard1 |
dc.subject |
Mitochondria |
dc.title |
Hypothalamic pregnenolone mediates recognition memory in the context of metabolic disorders |
dc.type |
Article |
dc.description.abstract |
Altres ajuts: "la Caixa" Foundation (ID100010434) under agreement LCF/PR/HR19/52160016. |
dc.description.abstract |
Obesity and type 2 diabetes are associated with cognitive dysfunction. Because 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 suggest 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 patients with obesity. Our data reveal 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. Ramírez et al. show that reduced hypothalamic pregnenolone levels, in the context of metabolic diseases, are associated with cognitive deterioration. POMC neuron-derived pregnenolone is a key mediator of cognition, but not metabolism, acting via hippocampal mechanisms. These results identify an unsuspected role for POMC neuron-derived pregnenolone in memory performance. |