Dietary omega-3 deficiency exacerbates inflammation and reveals spatial memory deficits in mice exposed to lipopolysaccharide during gestation

Abstract

Maternal immune activation (MIA) is a common environmental insult on the developing brain and represents a risk factor for neurodevelopmental disorders. Animal models of in utero inflammation further revealed a causal link between maternal inflammatory activation during pregnancy and behavioural impairment relevant to neurodevelopmental disorders in the offspring. Accumulating evidence point out that proinflammatory cytokines produced both in the maternal and fetal compartments are responsible for social, cognitive and emotional behavioral deficits in the offspring. Polyunsaturated fatty acids (PUFAs) are essential fatty acids with potent immunomodulatory activities. PUFAs and their bioactive derivatives can promote or inhibit many aspects of the immune and inflammatory response. PUFAs of the n-3 series ('n-3 PUFAs', also known as omega-3) exhibit anti-inflammatory/pro-resolution properties and promote immune functions, while PUFAs of the n-6 series ('n-6 PUFAs' or omega-6) favor pro-inflammatory responses. The present study aimed at providing insight into the effects of n-3 PUFAs on the consequences of MIA on brain development. We hypothesized that a reduction in n-3 PUFAs exacerbates both maternal and fetal inflammatory responses to MIA and later-life defects in memory in the offspring. Based on a lipopolysaccharide (LPS) model of MIA (LPS injection at embryonic day 17), we showed that n-3 PUFA deficiency 1) alters fatty acid composition of the fetal and adult offspring brain; 2) exacerbates maternal and fetal inflammatory processes with no significant alteration of microglia phenotype, and 3) induces spatial memory deficits in the adult offspring. We also showed a strong negative correlation between brain content in n-3 PUFA and cytokine production in MIA-exposed fetuses. Overall, our study is the first to address the deleterious effects of n-3 PUFA deficiency on brain lipid composition, inflammation and memory performances in MIA-exposed animals and indicates that it should be considered as a potent environmental risk factor for the apparition of neurodevelopmental disorders.

A More Comprehensive Approach to the Neuroprotective Potential of Long-Chain Polyunsaturated Fatty Acids in Preterm Infants Is Needed—Should We Consider Maternal Diet and the n-6:n-3 Fatty Acid Ratio?

“…At high levels of DHA and EPA, AA becomes suppressed (125), and correlation between low levels of AA and poor growth have been demonstrated (126). Rodent models of neonatal brain injury have demonstrated neuroprotective effects of DHA through several potential mechanisms (27,127,128). Labrousse et al demonstrated association between n-3 fatty acid deficiency and increased levels of cytokines (127).…”

miR‐203 accelerates apoptosis and inflammation induced by LPS via targeting NFIL3 in cardiomyocytes

“…[23][24][25] Inflammation is recognized to associate with various aspects of cardiovascular disease. [23][24][25] Inflammation is recognized to associate with various aspects of cardiovascular disease.…”

Inflammation (IL-1β) Modifies the Effect of Vitamin D and Omega-3 Long Chain Polyunsaturated Fatty Acids on Core Symptoms of Autism Spectrum Disorder—An Exploratory Pilot Study

“…Although the mechanistic pathways by which these nutrients may affect ASD is not clear, it has been hypothesised that the relationship between these nutrients and ASD can be partly mediated by inflammatory markers, as seen in other neuropsychiatric conditions where inflammation may contribute [46][47][48]. To the best of our knowledge, no studies have examined the potential modifying effect of participants' pre-treatment inflammatory state on vitamin D and omega-3 LCPUFA treatment response in children with ASD.…”