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Low Phytanic Acid-Concentrated DHA Prevents Cognitive Deficit and Regulates Alzheimer Disease Mediators in an ApoE−/− Mice Experimental Model

1
Department of Physiology, Faculty of Medicine, Complutense University, 28040 Madrid, Spain
2
Department of Psychobiology, Faculty of Psychology, Complutense University, 28223 Madrid, Spain
3
Department of Nutrition and Food Science, Faculty of Pharmacy, Complutense University, 28040 Madrid, Spain
4
Natac Pharma S.L., Alcorcón, 28923 Madrid, Spain
5
Natac Biotech S.L., Alcorcón, 28923 Madrid, Spain
*
Authors to whom correspondence should be addressed.
Both authors contributed equally to the study.
Nutrients 2019, 11(1), 11; https://doi.org/10.3390/nu11010011
Received: 21 November 2018 / Revised: 14 December 2018 / Accepted: 15 December 2018 / Published: 20 December 2018
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Abstract

Alzheimer’s disease (AD) is the main cause of dementia and cognitive impairment. It has been associated with a significant diminution of omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) levels in the brain. Clinical trials with DHA as a treatment in neurological diseases have shown inconsistent results. Previously, we reported that the presence of phytanic acid (PhA) in standard DHA compositions could be blunting DHA’s beneficial effects. Therefore, we aimed to analyze the effects of a low PhA-concentrated DHA and a standard PhA-concentrated DHA in Apolipoprotein E knockout (ApoE−/−) mice. Behavioral tests and protein expression of pro-inflammatory, pro-oxidant, antioxidant factors, and AD-related mediators were evaluated. Low PhA-concentrated DHA decreased Aβ, ß-amyloid precursor protein (APP), p-tau, Ca2+/calmodulin-dependent protein kinase II (CAMKII), caspase 3, and catalase, and increased brain derived neurotrophic factor (BDNF) when compared to standard PhA-concentrated DHA. Low PhA-concentrated DHA decreased interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α) protein expression in ApoE−/− mice when compared to standard PhA-concentrated DHA. No significant differences were found in p22phox, inducible nitric oxide synthase (iNOS), glutathione peroxidase (GPx), superoxide dismutase 1 (SOD-1), and tau protein expression. The positive actions of a low PhA-concentrated DHA were functionally reflected by improving the cognitive deficit in the AD experimental model. Therefore, reduction of PhA content in DHA compositions could highlight a novel pathway for the neurodegeneration processes related to AD. View Full-Text
Keywords: Alzheimer’s; DHA; ApoE−/−; phytanic acid; inflammation; neuroprotection; oxidation Alzheimer’s; DHA; ApoE−/−; phytanic acid; inflammation; neuroprotection; oxidation
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Ruiz-Roso, M.B.; Echeverry-Alzate, V.; Ruiz-Roso, B.; Quintela, J.C.; Ballesteros, S.; Lahera, V.; De las Heras, N.; López-Moreno, J.A.; Martín-Fernández, B. Low Phytanic Acid-Concentrated DHA Prevents Cognitive Deficit and Regulates Alzheimer Disease Mediators in an ApoE−/− Mice Experimental Model. Nutrients 2019, 11, 11.

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