TY - JOUR
T1 - Neuroprotective role of dietary supplementation with omega-3 fatty acids in the presence of basal forebrain cholinergic neurons degeneration in aged mice
AU - Cutuli, Debora
AU - Landolfo, Eugenia
AU - Decandia, Davide
AU - Nobili, Annalisa
AU - Viscomi, Maria Teresa
AU - La Barbera, Livia
AU - Sacchetti, Stefano
AU - De Bartolo, Paola
AU - Curci, Annacarmen
AU - D’amelio, Marcello
AU - Farioli-Vecchioli, Stefano
AU - Petrosini, Laura
N1 - Funding Information:
Funding: This research was funded by the Italian Ministry of Health, grant number GR-2011-02351086 (to D.C.) and Ricerca Corrente (to L.P.), and by the Alzheimer’s Association, grant number AARG-18-566270 (to M.D.A.).
Funding Information:
Acknowledgments: The present research has been supported by grants from the Italian Ministry of Health (Young Investigator’s Award: GR-2011-02351086 to D.C.; Ricerca Corrente to L.P.). M.D.A. was supported by grants from the Italian Ministry of Health (Research Grant: RF-2018-12365527) and from the Alzheimer’s Association (Grant: AARG-18-566270). A.N. was supported by Post-doctoral Fellowships by the Collegio Ghislieri. S.S. was supported by PhD Fellowships by the Department of Physiology and Pharmacology “V. Erspamer”, University of Rome “Sapienza”, 00185, Rome, Italy.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/3/1
Y1 - 2020/3/1
N2 - As major components of neuronal membranes, omega-3 polyunsaturated fatty acids (n-3 PUFA) exhibit a wide range of regulatory functions. Recent human and animal studies indicate that n-3 PUFA may exert beneficial effects on aging processes. Here we analyzed the neuroprotective influence of n-3 PUFA supplementation on behavioral deficits, hippocampal neurogenesis, volume loss, and astrogliosis in aged mice that underwent a selective depletion of basal forebrain cholinergic neurons. Such a lesion represents a valid model to mimic a key component of the cognitive deficits associated with dementia. Aged mice were supplemented with n-3 PUFA or olive oil (as isocaloric control) for 8 weeks and then cholinergically depleted with mu-p75-saporin immunotoxin. Two weeks after lesioning, mice were behaviorally tested to assess anxious, motivational, social, mnesic, and depressive-like behaviors. Subsequently, morphological and biochemical analyses were performed. In lesioned aged mice the n-3 PUFA pre-treatment preserved explorative skills and associative retention memory, enhanced neurogenesis in the dentate gyrus, and reduced volume and VAChT levels loss as well as astrogliosis in hippocampus. The present findings demonstrating that n-3 PUFA supplementation before cholinergic depletion can counteract behavioral deficits and hippocampal neurodegeneration in aged mice advance a low-cost, non-invasive preventive tool to enhance life quality during aging.
AB - As major components of neuronal membranes, omega-3 polyunsaturated fatty acids (n-3 PUFA) exhibit a wide range of regulatory functions. Recent human and animal studies indicate that n-3 PUFA may exert beneficial effects on aging processes. Here we analyzed the neuroprotective influence of n-3 PUFA supplementation on behavioral deficits, hippocampal neurogenesis, volume loss, and astrogliosis in aged mice that underwent a selective depletion of basal forebrain cholinergic neurons. Such a lesion represents a valid model to mimic a key component of the cognitive deficits associated with dementia. Aged mice were supplemented with n-3 PUFA or olive oil (as isocaloric control) for 8 weeks and then cholinergically depleted with mu-p75-saporin immunotoxin. Two weeks after lesioning, mice were behaviorally tested to assess anxious, motivational, social, mnesic, and depressive-like behaviors. Subsequently, morphological and biochemical analyses were performed. In lesioned aged mice the n-3 PUFA pre-treatment preserved explorative skills and associative retention memory, enhanced neurogenesis in the dentate gyrus, and reduced volume and VAChT levels loss as well as astrogliosis in hippocampus. The present findings demonstrating that n-3 PUFA supplementation before cholinergic depletion can counteract behavioral deficits and hippocampal neurodegeneration in aged mice advance a low-cost, non-invasive preventive tool to enhance life quality during aging.
KW - Aging
KW - Cholinergic system
KW - Cognitive deficits
KW - Neuroprotection
KW - Omega-3 fatty acids
KW - Prevention
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U2 - 10.3390/ijms21051741
DO - 10.3390/ijms21051741
M3 - Article
C2 - 32143275
AN - SCOPUS:85081029752
VL - 21
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 5
M1 - 1741
ER -