Fatty acid and phospholipase A2 plasma levels in children with autism

Tostes, Márcia Helena Fávero de Souza; Polonini, Hudson; Mendes, Rosemeri; Brandão, Marcos Antônio Fernandes; Gattaz, Wagner F.; Raposo, Nádia Rezende Barbosa

doi:10.1590/s2237-60892013000100009

Cited by 5 publications

(6 citation statements)

References 19 publications

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“…Total n -6/ n -3 LCPUFA ratio was reported in six studies, of which two reported ARA/EPA ratio [ 27 , 52 ], and one reported both ARA/EPA and ARA/DHA also [ 51 ]. Of the remaining studies, two reported the ratio of ARA/EPA [ 28 , 66 ] and ARA/DHA each [ 26 , 30 ], one both [ 53 ], and three no ratios [ 65 , 67 , 68 ]. Reverse ratios and SDs were calculated in five studies ([ 50 ] (only the ARA to EPA) and [ 49 , 51 , 52 , 53 ]).…”

Section: Resultsmentioning

confidence: 99%

“…Heterogeneity for EPA reduced slightly by removing the Parletta, 2016 study [ 52 ] ( I 2 = 74%, p = 0.0008). Removal of this study together with the Tostes, 2013 study [ 68 ] significantly reduced heterogeneity for EPA ( I 2 = 0%, p = 0.78) that was accompanied by a reduction in the difference between cases and controls (−0.30 [−0.51, −0.08], Z = 2.73, p = 0.006, n = 356). These two studies were different with respect to some characteristics that may affect outcomes compared to other studies; children with ASD were significantly younger than typically developing children in the Parletta, 2016 study [ 52 ], and 88% of children with ASD in the Tostes, 2013 study were on psychotropic drugs [ 68 ].…”

Section: Resultsmentioning

confidence: 99%

“…Psychotropic medications such as rispiradone may affect RBC fatty acid composition through their effect on oxidative stress and lipid peroxidation [ 23 , 74 ]. The Parletta, 2016 study [ 52 ] together with the Tostes, 2013 study [ 68 ] resulted in high levels of heterogeneity in EPA. ASD children in the former study were significantly younger than typically developing children [ 52 ], and approximately 88% of children with ASD in the Tostes, 2013 study were on psychotropic medication [ 68 ].…”

Section: Discussionmentioning

confidence: 99%

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Relationship between Long Chain n-3 Polyunsaturated Fatty Acids and Autism Spectrum Disorder: Systematic Review and Meta-Analysis of Case-Control and Randomised Controlled Trials

et al. 2017

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Omega-3 long chain polyunsaturated fatty acid supplementation (n-3 LCPUFA) for treatment of Autism Spectrum Disorder (ASD) is popular. The results of previous systematic reviews and meta-analyses of n-3 LCPUFA supplementation on ASD outcomes were inconclusive. Two meta-analyses were conducted; meta-analysis 1 compared blood levels of LCPUFA and their ratios arachidonic acid (ARA) to docosahexaenoic acid (DHA), ARA to eicosapentaenoic acid (EPA), or total n-6 to total n-3 LCPUFA in ASD to those of typically developing individuals (with no neurodevelopmental disorders), and meta-analysis 2 compared the effects of n-3 LCPUFA supplementation to placebo on symptoms of ASD. Case-control studies and randomised controlled trials (RCTs) were identified searching electronic databases up to May, 2016. Mean differences were pooled and analysed using inverse variance models. Heterogeneity was assessed using I2 statistic. Fifteen case-control studies (n = 1193) were reviewed. Compared with typically developed, ASD populations had lower DHA (−2.14 [95% CI −3.22 to −1.07]; p < 0.0001; I2 = 97%), EPA (−0.72 [95% CI −1.25 to −0.18]; p = 0.008; I2 = 88%), and ARA (−0.83 [95% CI, −1.48 to −0.17]; p = 0.01; I2 = 96%) and higher total n-6 LCPUFA to n-3 LCPUFA ratio (0.42 [95% CI 0.06 to 0.78]; p = 0.02; I2 = 74%). Four RCTs were included in meta-analysis 2 (n = 107). Compared with placebo, n-3 LCPUFA improved social interaction (−1.96 [95% CI −3.5 to −0.34]; p = 0.02; I2 = 0) and repetitive and restricted interests and behaviours (−1.08 [95% CI −2.17 to −0.01]; p = 0.05; I2 = 0). Populations with ASD have lower n-3 LCPUFA status and n-3 LCPUFA supplementation can potentially improve some ASD symptoms. Further research with large sample size and adequate study duration is warranted to confirm the efficacy of n-3 LCPUFA.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Relationship between Long Chain n-3 Polyunsaturated Fatty Acids and Autism Spectrum Disorder: Systematic Review and Meta-Analysis of Case-Control and Randomised Controlled Trials

et al. 2017

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“…We have previously reviewed the genetic and environmental risk factors that cause defects in the signalling of the COX‐PGE 2 pathway and lead to neurodevelopmental disorders such as ASD (Tamiji & Crawford, ; Wong et al ., , ). For example, various studies reported lower levels of arachidonic acid, abnormal levels and activity of PLA2, and increased levels of COX‐2 and PGE 2 in blood plasma of individuals with ASD (Bell et al ., , ; El‐Ansary et al ., ; Tostes et al ., ; Brigandi et al ., ; El‐Ansary et al ., ; Jory, ). These changes were correlated with abnormalities in sensory behaviours of ASD (El‐Ansary et al ., ).…”

Section: Introductionmentioning

confidence: 99%

Microarray analysis of gene expression in the cyclooxygenase knockout mice – a connection to autism spectrum disorder

Rai-Bhogal

Ahmad

et al. 2017

Eur J of Neuroscience

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The cellular and molecular events that take place during brain development play an important role in governing function of the mature brain. Lipid-signalling molecules such as prostaglandin E (PGE ) play an important role in healthy brain development. Abnormalities along the COX-PGE signalling pathway due to genetic or environmental causes have been linked to autism spectrum disorder (ASD). This study aims to evaluate the effect of altered COX-PGE signalling on development and function of the prenatal brain using male mice lacking cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2 ) as potential model systems of ASD. Microarray analysis was used to determine global changes in gene expression during embryonic days 16 (E16) and 19 (E19). Gene Ontology: Biological Process (GO:BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were implemented to identify affected developmental genes and cellular processes. We found that in both knockouts the brain at E16 had nearly twice as many differentially expressed genes, and affected biological pathways containing various ASD-associated genes important in neuronal function. Interestingly, using GeneMANIA and Cytoscape we also show that the ASD-risk genes identified in both COX-1 and COX-2 models belong to protein-interaction networks important for brain development despite of different cellular localization of these enzymes. Lastly, we identified eight genes that belong to the Wnt signalling pathways exclusively in the COX-2 mice at E16. The level of PKA-phosphorylated β-catenin (S552), a major activator of the Wnt pathway, was increased in this model, suggesting crosstalk between the COX-2-PGE and Wnt pathways during early brain development. Overall, these results provide further molecular insight into the contribution of the COX-PGE pathways to ASD and demonstrate that COX-1 and COX-2 animals might be suitable new model systems for studying the disorders.

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“…22,30,[35][36][37] Various abnormalities in key components of the COX2/PGE2 pathway due to both genetic and environmental influences have been implicated in clinical studies on ASD 20,21 (Figure 1). For instance, increased and decreased ratios of AA to omega-3 and omega-6 fatty acids, [38][39][40] increased PLA2 activity, 41 decreased total AA and increased PGE2 levels 42 have been reported in blood samples of human patients with ASD. Moreover, polymorphism of Ptgs2, the gene that encodes the COX2 enzyme, has been associated with ASD and its relevant behaviors.…”

mentioning

confidence: 99%

Autism‐related behaviors in the cyclooxygenase‐2‐deficient mouse model

Wong

Bestard-Lorigados

Crawford

2018

Genes Brain and Behavior

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Prostaglandin E2 (PGE2) is an endogenous lipid molecule involved in normal brain development. Cyclooxygenase-2 (COX2) is the main regulator of PGE2 synthesis. Emerging clinical and molecular research provides compelling evidence that abnormal COX2/PGE2 signaling is associated with autism spectrum disorder (ASD). We previously found that COX2 knockout mice had dysregulated expression of many ASD genes belonging to important biological pathways for neurodevelopment. The present study is the first to show the connection between irregular COX2/PGE2 signaling and autism-related behaviors in male and female COX2-deficient knockin, (COX)-2 , mice at young (4-6 weeks) or adult (8-11 weeks) ages. Autism-related behaviors were prominent in male (COX)-2 mice for most behavioral tests. In the open field test, (COX)-2 mice traveled more than controls and adult male (COX)-2 mice spent less time in the center indicating elevated hyperactive and anxiety-linked behaviors. (COX)-2 mice also buried more marbles, with males burying more than females, suggesting increased anxiety and repetitive behaviors. Young male (COX)-2 mice fell more frequently in the inverted screen test revealing motor deficits. The three-chamber sociability test found that adult female (COX)-2 mice spent less time in the novel mouse chamber indicative of social abnormalities. In addition, male (COX)-2 mice showed altered expression of several autism-linked genes: Wnt2, Glo1, Grm5 and Mmp9. Overall, our findings offer new insight into the involvement of disrupted COX2/PGE2 signaling in ASD pathology with age-related differences and greater impact on males. We propose that (COX)-2 mice might serve as a novel model system to study specific types of autism.

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Fatty acid and phospholipase A2 plasma levels in children with autism

Abstract: The study did not show a correlation between fatty acid and phospholipase A2 plasma levels and the developmental profile of children with autism.

Cited by 5 publications

References 19 publications

Relationship between Long Chain n-3 Polyunsaturated Fatty Acids and Autism Spectrum Disorder: Systematic Review and Meta-Analysis of Case-Control and Randomised Controlled Trials

Relationship between Long Chain n-3 Polyunsaturated Fatty Acids and Autism Spectrum Disorder: Systematic Review and Meta-Analysis of Case-Control and Randomised Controlled Trials

Microarray analysis of gene expression in the cyclooxygenase knockout mice – a connection to autism spectrum disorder

Autism‐related behaviors in the cyclooxygenase‐2‐deficient mouse model

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