title: Omega-3 polyunsaturated fatty acids improve mitochondrial dysfunction in brain aging--impact of Bcl-2 and NPD-1 like metabolites.
abstract: The present study investigated the effects of orally administered long chain omega-3 polyunsaturated fatty acids (PUFA) on mitochondrial function and processing of the amyloid precursor protein (APP) in brains of young (3 months old) and aged (24 months old) NMRI-mice. Neuroprotective properties of fish oil (FO) (1.6 ml/kg p.o.) were assessed ex vivo after 21 days in dissociated brain cells (DBC) and isolated mitochondria. Docosahexaenoic acid (DHA) levels were significantly lower in blood and brains of aged mice which were compensated by FO administration. Isolated DBC and mitochondria from aged mice showed significantly lower adenosine triphosphate (ATP) levels and reduced activity of complexes I+II and IV of the mitochondrial respiration system, respectively. FO restored the age-related decrease in respiration and improved ATP production. Moreover, FO increased the levels of anti-apoptotic Bcl-2 protein. Cell membrane fractions isolated from the brain of aged mice exhibited lower membrane fluidity, which was partially improved under FO treatment. In comparison to young animals, levels of neuroprotective sAPPα were significantly lower in the brain of aged mice. However, levels of sAPPα, Aβ and C-terminal APP fragments (CTF) were largely unchanged after FO treatment in aged mice. Neuroprotectin D-1 (NPD-1) represents a neuroprotective compound that is derived from unesterified DHA. Levels of NPD1-like metabolites (NPD1-like) and of unesterified DHA were significantly increased in brains of aged mice. FO treatment further strongly increased NPD1-like levels indicating an accelerated conversion rate of free DHA to NPD1-like. Our findings provide new mechanisms underlying the neuroprotective actions of omega-3 PUFA and identified FO as a promising nutraceutical to delay age-related mitochondrial dysfunction in the brain.
authors: Department of Pharmacology, Goethe-University of Frankfurt, D-60438 Frankfurt, Germany.
authors: Sarah
authors: S
authors: Afshordel
authors: Department of Pharmacology, Goethe-University of Frankfurt, D-60438 Frankfurt, Germany.
authors: Stephanie
authors: S
authors: Hagl
authors: Department of Pharmacology, Goethe-University of Frankfurt, D-60438 Frankfurt, Germany.
authors: Deborah
authors: D
authors: Werner
authors: Experimental Neurosurgery, Center for Neurology and Neurosurgery, Goethe-University Hospital, Neuroscience Center, D-60590 Frankfurt, Germany.
authors: Nelli
authors: N
authors: Röhner
authors: Experimental Neurosurgery, Center for Neurology and Neurosurgery, Goethe-University Hospital, Neuroscience Center, D-60590 Frankfurt, Germany.
authors: Donat
authors: D
authors: Kögel
authors: LSU Neuroscience Center And Department of Ophthalmology, Louisiana State University, Health Sciences Center, School of Medicine, New Orleans, LA 70112, USA.
authors: Nicolas G
authors: NG
authors: Bazan
authors: Department of Pharmacology, Goethe-University of Frankfurt, D-60438 Frankfurt, Germany. Electronic address: gunter.eckert@nutritional-neuroscience.com.
authors: Gunter P
authors: GP
authors: Eckert
mesh_terms: D000284:Administration, Oral; D000375:Aging; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D002478:Cells, Cultured; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D008560:Membrane Fluidity / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D015525:Fatty Acids, Omega-3; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; C487679:protectin D1; C052617:Bcl2 protein, mouse; D004281:Docosahexaenoic Acids
keywords: Aging; Bioenergetics; Brain; Docosahexaenoic acid; Fish oil; Omega-3 fatty acids