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Although adolescents are among the highest consumers of sweet foods, whether brain alterations induced by the sugar intake during this age persist until young adulthood or are rescued returning to a healthy diet remains largely unexplored. To shed light on this issue, just weaned rats were fed with a fructose-rich or control diet for 3\u00a0weeks. At the end of the treatment, fructose-fed rats underwent a control diet for a further 3\u00a0weeks until young adulthood phase and compared with animals that received from the beginning the healthy control diet. We focused on the consequences induced by the sugar on the main neurotrophins and neurotransmitters in the frontal cortex, as its maturation continues until late adolescence, thus being the last brain region to achieve a full maturity. We observed that fructose intake induces inflammation and oxidative stress, alteration of mitochondrial function, and changes of brain-derived neurotrophic factor (BDNF) and neurotrophin receptors, synaptic proteins, acetylcholine, dopamine, and glutamate levels, as well as increased formation of the glycation end-products <jats:italic>N\u03b5<\/jats:italic>-carboxymethyllysine (CML) and <jats:italic>N\u03b5<\/jats:italic>-carboxyethyllysine (CEL). Importantly, many of these alterations (BDNF, CML, CEL, acetylcholinesterase activity, dysregulation of neurotransmitters levels) persisted after switching to the control diet, thus pointing out to the adolescence as a critical phase, in which extreme attention should be devoted to limit an excessive consumption of sweet foods that can affect brain physiology also in the long term.<\/jats:p>","DOI":"10.1007\/s12035-022-03115-8","type":"journal-article","created":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T10:04:06Z","timestamp":1668679446000},"page":"1004-1020","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Long-Lasting Impact of Sugar Intake on Neurotrophins and Neurotransmitters from Adolescence to Young Adulthood in Rat Frontal Cortex"],"prefix":"10.1007","volume":"60","author":[{"given":"Maria Stefania","family":"Spagnuolo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Mazzoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Nazzaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio Dario","family":"Troise","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Gatto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Tonini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayra","family":"Colardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Segatto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Scaloni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Pallottini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna","family":"Iossa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5491-9659","authenticated-orcid":false,"given":"Luisa","family":"Cigliano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,17]]},"reference":[{"issue":"5","key":"3115_CR1","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1016\/j.jhep.2018.01.019","volume":"68","author":"T Jensen","year":"2018","unstructured":"Jensen T, Abdelmalek MF, Sullivan S, Nadeau KJ, Green M, Roncal C, Nakagawa T, Kuwabara M et al (2018) Fructose and sugar: a major mediator of non-alcoholic fatty liver disease. 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