JC#12.1 Hypothalamic pregnenolone mediates recognition memory in the context-Jakub Chwastek

🔎📰 Paper: Hypothalamic pregnenolone mediates recognition memory in the context of metabolic disorders. Sara Ramı´rez, Roberta Haddad-To´ volli, Marija Radosevic, Amanda Jime´ nez, Jose´ C. Ferna´ ndez-Checa, Marc Claret. Cell Metabolism. 2022 Feb 1. doi: 10.1016/j.cmet.2021.12.023 https://www.cell.com/cell-metabolism/.... 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. Critical assessment of this research publication is for scientific/education purposes only. 🌐COIL Program: This video belongs to the Collaborative Online International Learning (COIL) Program of SJTU, which aims to create international collaborations between labs to enhance students' presentation skills and foster critical thinking. For the semester running from February 2024 to July 2024 ivLab @ Shanghai Jiao Tong University is collaborating with Dr. Witold Konopka's Neuroplasticity and Metabolism Research Group from Poland. ivLab @ Shanghai Jiao Tong University http://vinnikov.science https://x.com/vinnikovLAB