Ramirez, Sara, Haddad-Tovolli, Roberta ORCID: 0000-0002-1739-3205, Radosevic, Marija ORCID: 0000-0002-8323-6160, Toledo, Miriam ORCID: 0000-0002-1332-7454, Pane, Adriana ORCID: 0000-0002-7810-1827, Alcolea, Daniel ORCID: 0000-0002-3819-3245, Ribas, Vicent ORCID: 0000-0003-3380-2256, Mila-Guasch, Maria, Pozo, Macarena, Obri, Arnaud ORCID: 0000-0002-0779-1082, Eyre, Elena, Gomez-Valades, Alicia G., Chivite, Inigo, Van Eeckhout, Tomas, Zalachoras, Ioannis ORCID: 0000-0002-8113-3512, Altirriba, Jordi, Bauder, Corinna, Imbernon, Monica, Garrabou, Gloria ORCID: 0000-0001-8973-9933, Garcia-Ruiz, Carmen, Nogueiras, Ruben, Soto, David, Gasull, Xavier, Sandi, Carmen, Bruening, Jens C., Fortea, Juan ORCID: 0000-0002-1340-638X, Jimenez, Amanda ORCID: 0000-0003-4967-1174, Fernandez-Checa, Jose C. and Claret, Marc ORCID: 0000-0001-7766-9296 (2022). Hypothalamic pregnenolone mediates recognition memory in the context of metabolic disorders. Cell Metab., 34 (2). S. 269 - 294. CAMBRIDGE: CELL PRESS. ISSN 1932-7420

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Ramirez, SaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haddad-Tovolli, RobertaUNSPECIFIEDorcid.org/0000-0002-1739-3205UNSPECIFIED
Radosevic, MarijaUNSPECIFIEDorcid.org/0000-0002-8323-6160UNSPECIFIED
Toledo, MiriamUNSPECIFIEDorcid.org/0000-0002-1332-7454UNSPECIFIED
Pane, AdrianaUNSPECIFIEDorcid.org/0000-0002-7810-1827UNSPECIFIED
Alcolea, DanielUNSPECIFIEDorcid.org/0000-0002-3819-3245UNSPECIFIED
Ribas, VicentUNSPECIFIEDorcid.org/0000-0003-3380-2256UNSPECIFIED
Mila-Guasch, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pozo, MacarenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Obri, ArnaudUNSPECIFIEDorcid.org/0000-0002-0779-1082UNSPECIFIED
Eyre, ElenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gomez-Valades, Alicia G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chivite, InigoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Van Eeckhout, TomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zalachoras, IoannisUNSPECIFIEDorcid.org/0000-0002-8113-3512UNSPECIFIED
Altirriba, JordiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bauder, CorinnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Imbernon, MonicaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garrabou, GloriaUNSPECIFIEDorcid.org/0000-0001-8973-9933UNSPECIFIED
Garcia-Ruiz, CarmenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nogueiras, RubenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Soto, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gasull, XavierUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sandi, CarmenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruening, Jens C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fortea, JuanUNSPECIFIEDorcid.org/0000-0002-1340-638XUNSPECIFIED
Jimenez, AmandaUNSPECIFIEDorcid.org/0000-0003-4967-1174UNSPECIFIED
Fernandez-Checa, Jose C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Claret, MarcUNSPECIFIEDorcid.org/0000-0001-7766-9296UNSPECIFIED
URN: urn:nbn:de:hbz:38-696000
DOI: 10.1016/j.cmet.2021.12.023
Journal or Publication Title: Cell Metab.
Volume: 34
Number: 2
Page Range: S. 269 - 294
Date: 2022
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1932-7420
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
POMC NEURONS; EXPRESSING NEURONS; TRANSGENIC MICE; INSULIN; PROTEIN; STRESS; IMPAIRMENT; RESISTANCE; PHENOTYPE; RELEASEMultiple languages
Cell Biology; Endocrinology & MetabolismMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/69600

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