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

• Published in: The FASEB journal Vol. 34; no. 2; pp. 2024 - 2040
• Main Authors: Talamonti, Emanuela, Sasso, Valeria, To, Hoi, Haslam, Richard P., Napier, Johnathan A., Ulfhake, Brun, Pernold, Karin, Asadi, Abolfazl, Hessa, Tara, Jacobsson, Anders, Chiurchiù, Valerio, Viscomi, Maria Teresa
• Format: Journal Article
• Language: English
• Published: United States John Wiley and Sons Inc 01-02-2020
• Subjects: Animals; anti-inflammatory molecules; Biomarkers - metabolism; Brain - metabolism; Brain - pathology; brain plasticity; Brain-Derived Neurotrophic Factor - biosynthesis; Brain-Derived Neurotrophic Factor - genetics; Caspase 1 - biosynthesis; Caspase 1 - genetics; Docosahexaenoic Acids - biosynthesis; Docosahexaenoic Acids - genetics; Early Growth Response Protein 1 - biosynthesis; Early Growth Response Protein 1 - genetics; Fatty Acid Elongases - deficiency; Fatty Acid Elongases - metabolism; Gene Expression Regulation; Inflammation - genetics; Inflammation - metabolism; Interleukin-1beta - biosynthesis; Interleukin-1beta - genetics; Medicin och hälsovetenskap; Mice; Mice, Knockout; microglia; Microglia - metabolism; Microglia - pathology; Neuronal Plasticity; omega-3; PUFA; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - genetics; omega-3; PUFA; microglia; anti-inflammatory molecules; brain plasticity
• ISSN: 0892-6638; 1530-6860; 1530-6860
• DOI: 10.1096/fj.201901890RR

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.