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United States Department of Agriculture

Agricultural Research Service

Research Project: NEUROCOGNITION/NEUROSCIENCE

Location: Human Nutrition Research Center on Aging

Title: The ability of walnut extract and fatty acids to protect against the deleterious effects of oxidative stress and inflammation in hippocampal cells

Authors
item Carey, Amanda
item Fisher, Derek
item Joseph, James -
item Shukitt-Hale, Barbara

Submitted to: Nutritional Neuroscience
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 22, 2012
Publication Date: January 28, 2013
Citation: Carey, A.N., Fisher, D.R., Joseph, J.J., Shukitt Hale, B. 2013. The ability of walnut extract and fatty acids to protect against the deleterious effects of oxidative stress and inflammation in hippocampal cells. Nutritional Neuroscience. 16(1):13-20.

Interpretive Summary: Previous research has demonstrated that dietary walnut supplementation protects against age-related cognitive and motor function declines in rats. Although it is known that polyunsaturated fatty acids (PUFAs), which are found in walnuts, aid in maintaining healthy cell membranes and improve communication between cells, the cellular mechanisms by which walnuts and PUFAs may affect the health and functioning of neurons are undetermined. It has been postulated that at least part of the loss of cognitive function in aging may be the result of oxidative stress-induced loss of cellular calcium (Ca2+) buffering ability, which can result in cell death. Therefore, we assessed if pretreatment of hippocampal neurons with walnut extract or PUFAs (ALA, LA, EPA or DHA) would protect cells against oxidative stress-mediated cell death and Ca2+ dysregulation. Results indicated that walnut extract, ALA, and DHA provided significant protection against cell death and Ca2+ dysregulation. LA and EPA were not as effective at protecting neurons from these insults. Overall, this study suggests that PUFAs may protect against age-related cellular dysfunction via antioxidant and anti-inflammatory mechanisms and demonstrates that not all PUFAs are equivalent in their beneficial effects.

Technical Abstract: Walnuts contain polyunsaturated fatty acids (PUFAs), specifically the omega-6 fatty acid linoleic acid (LA) as well as the omega-3 fatty acid, alpha-linolenic acid (ALA), which can be metabolized to generate eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Previous research from our lab has demonstrated that dietary walnut supplementation protects against age-related cognitive and motor function declines in rats. Although it is known that PUFAs participate in structural maintenance of cell membranes, generation of second messengers and signaling molecules, and modulation of neurotransmitter activity, the cellular mechanisms by which walnuts and PUFAs may affect neuronal health and functioning in aging are undetermined. It has been postulated that at least part of the loss of cognitive function in aging may be the result of oxidative stress-induced loss of cellular calcium (Ca2+) buffering ability, which can result in cell death. Therefore, we assessed if pretreatment of primary hippocampal neurons with walnut extract or PUFAs (ALA, LA, EPA or DHA) would protect cells against dopamine (DA)- and lipopolysaccharide (LPS)-mediated cell death and Ca2+ dysregulation. Results indicated that walnut extract, ALA, and DHA provided significant protection against cell death and Ca2+ dysregulation; the effects were pretreatment concentration-dependent and stressor-dependent. LA and EPA were not as effective at protecting hippocampal cells from these insults. Overall, this study suggests that PUFAs may protect against age-related cellular dysfunction via antioxidant and anti-inflammatory mechanisms and demonstrates that not all PUFAs are equivalent in their beneficial effects.

Last Modified: 10/1/2014