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Insufficient leptin or leptin receptor (LepR) is involved in the disease pathogenesis. Leptin is involved with several neurological processes, and it has crucial developmental roles. We have previously demonstrated that leptin deficiency in early life leads to permanent developmental problems in young adult mice, including an imbalance in energy homeostasis, alterations in melanocortin and the reproductive system and a reduction in brain mass. Given that in humans, obesity has been associated with brain atrophy and cognitive impairment, it is important to determine the long-term consequences of early-life leptin deficiency on brain structure and memory function.<\/jats:p>\n               <jats:p>Here, we demonstrate that leptin-deficient (LepOb) mice exhibit altered brain volume, decreased neurogenesis and memory impairment. Similar effects were observed in animals that do not express the LepR (LepRNull). Interestingly, restoring the expression of LepR in 10-week-old mice reverses brain atrophy, in addition to neurogenesis and memory impairments in older animals.<\/jats:p>\n               <jats:p>Our findings indicate that leptin deficiency impairs brain development and memory, which are reversible by restoring leptin signalling in adulthood.<\/jats:p>","DOI":"10.1093\/brain\/awae127","type":"journal-article","created":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T07:27:48Z","timestamp":1713857268000},"page":"2706-2717","source":"Crossref","is-referenced-by-count":11,"title":["Leptin receptor reactivation restores brain function in early-life <i>Lepr<\/i>-deficient mice"],"prefix":"10.1093","volume":"147","author":[{"given":"Caroline","family":"Fernandes","sequence":"first","affiliation":[{"name":"Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro , Rio de Janeiro, RJ 21941-902 , Brazil"},{"name":"Institute of Biomedical Sciences, Federal University of Rio de Janeiro , Rio de Janeiro, RJ 21941-590 , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia","family":"Forny-Germano","sequence":"additional","affiliation":[{"name":"Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro , Rio de Janeiro, RJ 21941-902 , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayara M","family":"Andrade","sequence":"additional","affiliation":[{"name":"Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro , Rio de Janeiro, RJ 21941-902 , Brazil"},{"name":"Institute of Biomedical Sciences, Federal University of Rio de Janeiro , Rio de Janeiro, RJ 21941-590 , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia M","family":"Lyra E Silva","sequence":"additional","affiliation":[{"name":"Centre for Neuroscience Studies, Department of Biomedical and Molecular Sciences & Department of Psychiatry, Queen\u2019s University , Kingston, ON K7L 3N6 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela M","family":"Ramos-Lobo","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of S\u00e3o Paulo , S\u00e3o Paulo, SP 05508-000 , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda","family":"Meireles","sequence":"additional","affiliation":[{"name":"D\u2019Or Institute for Research and Education , Rio de Janeiro, RJ 22281-100 , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda","family":"Tovar-Moll","sequence":"additional","affiliation":[{"name":"D\u2019Or Institute for Research and Education , Rio de Janeiro, RJ 22281-100 , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Christophe","family":"Houzel","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, Federal University of Rio de Janeiro , Rio de Janeiro, RJ 21941-590 , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Jose","family":"Donato","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of S\u00e3o Paulo , S\u00e3o Paulo, SP 05508-000 , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8358-0589","authenticated-orcid":false,"given":"Fernanda G","family":"De Felice","sequence":"additional","affiliation":[{"name":"Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro , Rio de Janeiro, RJ 21941-902 , Brazil"},{"name":"Centre for Neuroscience Studies, Department of Biomedical and Molecular Sciences & Department of Psychiatry, Queen\u2019s University , Kingston, ON K7L 3N6 , Canada"},{"name":"D\u2019Or Institute for Research and Education , Rio de Janeiro, RJ 22281-100 , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,4,23]]},"reference":[{"key":"2024080113034627500_awae127-B1","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/S2213-8587(20)30118-2","article-title":"Type 2 diabetes and cognitive dysfunction\u2014Towards effective management of both comorbidities","volume":"8","author":"Srikanth","year":"2020","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2024080113034627500_awae127-B2","doi-asserted-by":"crossref","first-page":"104580","DOI":"10.1016\/j.nbd.2019.104580","article-title":"Obesity-related cognitive impairment: The role of endothelial dysfunction","volume":"132","author":"Buie","year":"2019","journal-title":"Neurobiol Dis"},{"key":"2024080113034627500_awae127-B3","doi-asserted-by":"crossref","first-page":"367","DOI":"10.2147\/CIA.S192050","article-title":"Associations between obesity and cognitive impairment in the Chinese elderly: An observational 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