Impairment of DHA synthesis alters the expression of neuronal plasticity markers and the brain inflammatory status in mice

A - Papers appearing in refereed journals

Talamonti, E., Sasso, V., To, H., Haslam, R. P., Napier, J. A., Ulfhake, B., Pernold, K., Asadi, A., Hessa, T., Jacobsson, A., Chiurchiu, V. and Viscomi, M. T. 2020. Impairment of DHA synthesis alters the expression of neuronal plasticity markers and the brain inflammatory status in mice. The FASEB Journal. 34 (2), pp. 2024-2040. https://doi.org/10.1096/fj.201901890RR

AuthorsTalamonti, E., Sasso, V., To, H., Haslam, R. P., Napier, J. A., Ulfhake, B., Pernold, K., Asadi, A., Hessa, T., Jacobsson, A., Chiurchiu, V. and Viscomi, M. T.
Abstract

Docosahexaenoic acid (DHA) is a ω-3 fatty acid typically obtained from the diet or endogenously synthesized through the action of elongases (ELOVLs) and desaturases. DHA is a key central nervous system constituent and the precursor of several molecules that regulate the resolution of inflammation. In the present study, we questioned whether the impaired synthesis of DHA affected neural plasticity and inflammatory status in the adult brain. To address this question, we investigated neural and inflammatory markers from mice deficient for ELOVL2 (Elovl2−/−), the key enzyme in DHA synthesis. From our findings, Elovl2−/− mice showed an altered expression of markers involved in synaptic plasticity, learning, and memory formation such as Egr-1, Arc1, and BDNF specifically in the cerebral cortex, impacting behavioral functions only marginally. In parallel, we also found that DHA-deficient mice were characterized by an increased expression of pro-inflammatory molecules, namely TNF, IL-1β, iNOS, caspase-1 as well as the activation and morphologic changes of microglia in the absence of any brain injury or disease. Reintroducing DHA in the diet of Elovl2−/− mice reversed such alterations in brain plasticity and inflammation. Hence, impairment of systemic DHA synthesis can modify the brain inflammatory and neural plasticity status, supporting the view that DHA is an essential fatty acid with an important role in keeping inflammation within its physiologic boundary and in shaping neuronal functions in the central nervous system.

KeywordsAnti-inflammatory molecules; Brain plasticity; Microglia; Omega-3; PUFA
Year of Publication2020
JournalThe FASEB Journal
Journal citation34 (2), pp. 2024-2040
Digital Object Identifier (DOI)https://doi.org/10.1096/fj.201901890RR
Open accessPublished as ‘gold’ (paid) open access
FunderBiotechnology and Biological Sciences Research Council
Funder project or codeTailoring Plant Metabolism ISP
Publisher's version
Output statusPublished
Publication dates
Online11 Dec 2019
Publication process dates
Accepted04 Nov 2019
PublisherThe Federation of American Societies for Experimental Biology
ISSN1530-6860

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