Behavioral, neuromorphological, and neurobiochemical effects induced by omega-3 fatty acids following basal forebrain ch
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(2020) 12:150
RESEARCH
Open Access
Behavioral, neuromorphological, and neurobiochemical effects induced by omega-3 fatty acids following basal forebrain cholinergic depletion in aged mice Debora Cutuli1,2* , Eugenia Landolfo1,2, Annalisa Nobili1,3, Paola De Bartolo1,4, Stefano Sacchetti2, Doriana Chirico5, Federica Marini6,7, Luisa Pieroni1, Maurizio Ronci8, Marcello D’Amelio1,3, Francesca Romana D’Amato5, Stefano Farioli-Vecchioli5† and Laura Petrosini1† Abstract Background: In recent years, mechanistic, epidemiologic, and interventional studies have indicated beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) against brain aging and age-related cognitive decline, with the most consistent effects against Alzheimer’s disease (AD) confined especially in the early or prodromal stages of the pathology. In the present study, we investigated the action of n-3 PUFA supplementation on behavioral performances and hippocampal neurogenesis, volume, and astrogliosis in aged mice subjected to a selective depletion of basal forebrain cholinergic neurons. Such a lesion represents a valuable model to mimic one of the most reliable hallmarks of early AD neuropathology. Methods: Aged mice first underwent mu-p75-saporin immunotoxin intraventricular lesions to obtain a massive cholinergic depletion and then were orally supplemented with n-3 PUFA or olive oil (as isocaloric control) for 8 weeks. Four weeks after the beginning of the dietary supplementation, anxiety levels as well as mnesic, social, and depressive-like behaviors were evaluated. Subsequently, hippocampal morphological and biochemical analyses and n-3 PUFA brain quantification were carried out. Results: The n-3 PUFA treatment regulated the anxiety alterations and reverted the novelty recognition memory impairment induced by the cholinergic depletion in aged mice. Moreover, n-3 PUFA preserved hippocampal volume, enhanced neurogenesis in the dentate gyrus, and reduced astrogliosis in the hippocampus. Brain levels of n-3 PUFA were positively related to mnesic abilities. (Continued on next page)
* Correspondence: [email protected]; [email protected] Authors Eugenia Landolfo and Stefano Sacchetti are part of the PhD Program in Behavioral Neuroscience. † Stefano Farioli-Vecchioli and Laura Petrosini contributed equally to this work. 1 IRCCS Fondazione Santa Lucia, Rome, Italy 2 University of Rome “Sapienza”, Rome, Italy Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If mate
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