Autism as a disorder of deficiency of brain-derived neurotrophic factor and altered metabolism of polyunsaturated fatty acids

Das, Undurti N.

doi:10.1016/j.nut.2013.01.012

Cited by 75 publications

(49 citation statements)

References 133 publications

(172 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These data further suggest that a dysregulation of eCB signaling might be driven by diet, resulting in an imbalance of pro-and anti-inflammatory metabolites, and thus favoring the development of autism [114].…”

Section: Alterations Of the Ecb System In Autismmentioning

confidence: 74%

Endocannabinoid Signaling in Autism

et al. 2015

View full text Add to dashboard Cite

Autism spectrum disorder (ASD) is a complex behavioral condition with onset during early childhood and a lifelong course in the vast majority of cases. To date, no behavioral, genetic, brain imaging, or electrophysiological test can specifically validate a clinical diagnosis of ASD. However, these medical procedures are often implemented in order to screen for syndromic forms of the disorder (i.e., autism comorbid with known medical conditions). In the last 25 years a good deal of information has been accumulated on the main components of the Bendocannabinoid (eCB) system^, a rather complex ensemble of lipid signals (Bendocannabinoids^), their target receptors, purported transporters, and metabolic enzymes. It has been clearly documented that eCB signaling plays a key role in many human health and disease conditions of the central nervous system, thus opening the avenue to the therapeutic exploitation of eCB-oriented drugs for the treatment of psychiatric, neurodegenerative, and neuroinflammatory disorders. Here we present a modern view of the eCB system, and alterations of its main components in human patients and animal models relevant to ASD. This review will thus provide a critical perspective necessary to explore the potential exploitation of distinct elements of eCB system as targets of innovative therapeutics against ASD.Key Words Autism spectrum disorder . endocannabinoid system . fragile X syndrome . metabolic regulation . reward system The Endocannabinoid SystemTwenty-five years after the cloning and expression of a complementary DNA that encoded a G protein-coupled receptor, named type-1 cannabinoid (CB 1 ) receptor [1], there is a good deal of information on the main components of the so-called Bendocannabinoid (eCB) system^, as well as on its role in controlling cannabinergic signaling in human health and disease [2][3][4]. Anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are the most active eCBs as yet identified, although this family of bioactive lipids includes other arachidonic acid (AA) derivatives with cannabimimetic properties (i.e., noladin ether, virodhamine, N-arachidonoyldopamine, to name but a few). The classical dogma that eCBs are synthesized and released Bon demand^upon (patho)physiological stimuli has been recently revisited on the basis of unexpected evidence for intracellular reservoirs and transporters of eCBs. These new entities have been shown to drive intracellular trafficking of eCBs, adding a new dimension to the regulation of their biological activity [5]. To date, several metabolic routes have B. Chakrabarti, A. Persico and N. Battista are equal first authors.

show abstract

Section: Alterations Of the Ecb System In Autismmentioning

confidence: 74%

Endocannabinoid Signaling in Autism

et al. 2015

View full text Add to dashboard Cite

show abstract

“…It is noteworthy that BDNF expression and DNA methylation are altered in several psychiatric disorders that are associated with early-life adversity, including depression, schizophrenia, bipolar disorder, and autism. BDNF is also involved in the pathogenesis of obesity, type 2 diabetes mellitus and metabolic syndrome (42) (resveratrol) may have the ability to augment BDNF synthesis and action since BDNF also has similar beneficial actions in these diseases (42,46). In a recent study, we noted that BDNF levels are low in subjects with type 2 diabetes mellitus (47) and that it interacts and enhances the production of an anti-inflammatory bioactive lipid namely, lipoxin A4, whose levels are also low in diabetes mellitus (47)(48)(49).…”

Section: Resveratrol Is Cytoprotective In Naturementioning

confidence: 99%

Beneficial action of resveratrol: How and why?

et al. 2016

View full text Add to dashboard Cite

Flavonoid resveratrol modulates the transcription factor NF-κB; inhibits the cytochrome P450 isoenzyme CYP1 A1; suppresses the expression and activity of cyclooxygenase enzymes; and modulates Fas/Fas-ligand-mediated apoptosis, p53, mammalian target of rapamycin, and cyclins and various phosphodiesterases. This increases the cytosolic cAMP that activates Epac1/CaMKKβ/AMPK/SIRT1/PGC-1α pathway, which in turn facilitates increased oxidation of fatty acids, mitochondrial biogenesis, mitochondrial respiration, and gluconeogenesis. Resveratrol triggers apoptosis of activated T cells and suppresses tumor necrosis factor-α, interluekin-17 (IL-17), and other proinflammatory molecules, and thus is of benefit in autoimmune diseases. In addition, resveratrol inhibits expression of hypoxia-inducible factor-1α and vascular endothelial growth factor, explaining its effective action against cancer. Brain-derived neurotrophic factor (BDNF) that is involved in the pathogenesis of obesity, type 2 diabetes mellitus, and metabolic syndrome is also altered in depression, schizophrenia, bipolar disorder, and autism. We noted that BDNF protects against cytotoxic actions of alloxan, streptozotocin, and benzo(a)pyrene. Resveratrol prevents bisphenol A-induced autism, type 2 diabetes mellitus, and metabolic syndrome, suggesting that it may augment BDNF synthesis and action. We also observed that BDNF levels are low in type 2 diabetes mellitus and that BDNF enhances production of antiinflammatory lipid, lipoxin A4, whose levels are low in diabetes mellitus. Thus, resveratrol may augment production of lipoxin A4. Resveratrol alters gut microbiota and influences stem cell proliferation and differentiation. These pleiotropic actions of resveratrol may explain the multitude of its actions and benefits.

show abstract

“…Micronutrients deficiency plays an important role on neurotrophic factors and neurotransmitters synthesis and effects. Even if the mechanism remains unclear, adverse events occurring prenatally such as malnutrition could also induce an excessive inflammatory response partly responsible for brain disorders [61].…”

Section: Dha and Other Fetal Disordersmentioning

confidence: 99%

Maternal and fetal benefits of DHA supplementation during pregnancy

Hubinont¹,

Savoye²

2017

J Pregnancy Reprod

View full text Add to dashboard Cite

During pregnancy, the benefits of long-chain n-3 fatty acids, mainly DHA supplementation has been reported with controversial results. The aim of this review paper is to clarify the role of DHA on maternal and fetal outcomes and to discuss supplementation.Low maternal concentrations of DHA are associated with an increased incidence of preeclampsia, gestational diabetes, postpartum depression, preterm labour and intrauterine fetal growth restriction (IUGR).The effect of a preventive supplementation on these complications is not clearly demonstrated . Some authors report an improved outcome but recent Cochrane database systematic reviews and meta-analysis are not conclusive.DHA supplementation reduces significantly the effects of prenatal stress and the perinatal mortality rate. In patients with previous history of preterm birth, supplementation is also controversial.In conclusion, even if the DHA requirements are increased in pregnancy and if positive correlations are reported between low maternal concentrations and an adverse pregnancy outcome, there are conflicting results on the efficacy of a DHA supplementation. Further studies using different DHA regimens of administration are needed. In the meantime, as it is a safe supplementation with few side effects, DHA should be prescribed in patients with a low dietary intake and risks factors.

show abstract

Autism as a disorder of deficiency of brain-derived neurotrophic factor and altered metabolism of polyunsaturated fatty acids

Cited by 75 publications

References 133 publications

Endocannabinoid Signaling in Autism

Endocannabinoid Signaling in Autism

Beneficial action of resveratrol: How and why?

Maternal and fetal benefits of DHA supplementation during pregnancy

Contact Info

Product

Resources

About