Elsevier

Clinical Nutrition

Volume 30, Issue 4, August 2011, Pages 407-415
Clinical Nutrition

Review
What you eat is what you are – A role for polyunsaturated fatty acids in neuroinflammation induced depression?

https://doi.org/10.1016/j.clnu.2011.03.013Get rights and content

Summary

As essential polyunsaturated fatty acids (PUFAs) influence both inflammatory and depressive disorders, nutrition related treatment methods deserve great research interest. However, currently biological mechanisms underlying the depression modulating effects of the PUFA Omega-3 (ω-3) and Omega-6 (ω-6) derived eicosanoids (central nervous system messengers) are not fully established. Depression related naturally occurring cell death (apoptosis) is thought to be mediated by excitotoxicity and free radicals that appear in the brain immediately following any inflammatory or ischemic damage, and increases the likelihood of clinically defined depression. This review explores the hypothesis that the interaction between ω-6 and ω-3 derived eicosanoids plays a central role in control over apoptosis linked with inflammation and inflammation-driven depression, via regulation of apoptosis inducing factors including excitotoxicity and free radicals.

Section snippets

Inflammation and depression

Inflammatory disorders such as myocardial infarction are associated with unusually high levels of depressive disorder.1 Clinical studies show that 20% of individuals develop major depressive disorder within 18 months of myocardial infarction, while 65% experience depressive episodes.2 Pooled estimates reveal that at least one third of stroke survivors also experience clinical depression3, 4 compared to 13% of the control population.4 To date, the reasons why inflammatory conditions are

Polyunsaturated fatty acids (PUFAs)

PUFAs are dietary lipids found in cell membranes, most abundantly in the central nervous system.14 Structurally, PUFAs are those essential fatty acids containing two or more double bonds, or carbon atoms capable of bonding to two or more hydrogen atoms. The number of carbon atoms determines the length of the fatty acid chain. Short-chain essential fatty acids, containing 18 or less carbons, serve as a substrate for the more biologically active longer chain fatty acids, which contain 20 or more

PUFAs and apoptosis

PUFAs are widely acknowledged to influence cell death and are neuroprotective at optimal doses.11 In cultured cells AA and LA inhibit apoptosis at doses of 10 μg,11 while EPA inhibits cell death at doses of 10 μg–40 μg11, 29, 88 DHA reduces apoptosis at doses of 5, 10, 20, 25 and 50 μg after 24 h of incubation11, 88, 89, 90 and at doses of 25 μg and 0.5 lM after 48 h.56, 91 Human studies also confirm that 2 weeks of DHA (400, 800 mg) supplementation reduces apoptosis in monocytes of healthy

PUFAs and excitotoxicity

Inflammatory conditions are coupled with a high occurrence of excitotoxic cell death.102, 103 Excitotoxicity is a glutamate driven necrotic form of neuronal cell death104 associated with excessive intracellular calcium (Ca2+) influx105 and the induction of downstream apoptosis.106 In vitro cell culture studies reveal excitotoxicity associated intracellular Ca2+influx which results in the release of inflammatory ω-6 AA.107, 108 Arachidonic acid (AA) acts to potentiate Ca2+ sensitive N-methyl-d

Future directions and conclusions

Given the regulatory role of cytokines in mediating intrinsic apoptotic pathways and the association between apoptosis and depression,8, 9 it is not surprising that inflammatory conditions are associated with unusually high levels of clinical depression.4 Omega-3 PUFAs that have immune modulating properties are also capable of inhibiting cytokine activity suggesting that increasing the consumption of ω-3 comparative to ω-6 shifts the production of eicosanoids away from those with potent

Statement of authorship

The authors’ responsibilities were as follows—MCP, SGC, LMC, DPC: contributed to the conception and design of the manuscript, MCP, SGC: contributed to the literature search, and interpretation of data; MCP: wrote the manuscript; and SGC, LMC, DPC: critically appraised the manuscript.

Disclosure/Conflict of interest

The authors declare no conflict of interest.

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