Study of the serum levels of polyunsaturated fatty acids and the expression of related liver metabolic enzymes in a rat valproate‐induced autism model

Zhao, Gang; Gao, Jingli; Liang, Shuang; Wang, Xuelai; Sun, Chongde; Hao, Yanqiu; Li, Xiang; Cao, Yonggang; Wu, Lijie

doi:10.1016/j.ijdevneu.2015.04.350

Cited by 12 publications

(8 citation statements)

References 34 publications

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“…The sex of the rodents influences behavioural outcomes in studies that consisted of both males and females. VPA exposure appeared to have no effect or a lesser effect in females [36][37][38][39][40], indicating females possess some resistance to social impairment induced by VPA, as opposed to males [41].…”

Section: Object-conspecific Testsmentioning

confidence: 87%

A Systematic Review of the Valproic-Acid-Induced Rodent Model of Autism

et al. 2020

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Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterised by repetitive behaviours, cognitive rigidity/inflexibility, and social-affective impairment. Unfortunately, few pharmacological treatments exist to alleviate these socio-behavioural impairments. Prenatal administration of valproic acid (VPA) has become an accepted animal model of ASD and has been extensively used to explore new pharmacotherapies in rodents. We conducted a systematic review of the behavioural impairments induced by the VPA model in rodents, with specific reference to 3 core socio-behavioural alterations associated with ASD: repetitive behaviours, cognitive rigidity/inflexibility, and social-affective impairment. We systematically reviewed studies attempting to alleviate these core behavioural alterations using pharmacological means. We include 132 studies exploring the prenatal effects of VPA in rodents. Gestational exposure to VPA in rodents has significant effects on rodent-equivalent measures of the 3 core behavioural traits characteristic of ASD in humans, inducing social impairments, repetitive behaviour, and cognitive rigidity/inflexibility after birth. This model's validity has seen it used to test potential drug treatments for ASD and is likely to continue doing so. We conclude the rodent VPA model may be suitable to examine future therapeutic interventions for ASD, providing an overview of the progress made so far.

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Section: Object-conspecific Testsmentioning

confidence: 87%

A Systematic Review of the Valproic-Acid-Induced Rodent Model of Autism

et al. 2020

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“…Then, the following animal experiments, we strictly controlled dietary conditions in both groups in order to reduce the effects of dietary factors, and we still found that serum n-3 and n-6 PUFA levels were lower in ASD model rats relative to controls. Moreover, we observed that the expression of rate-limiting PUFA metabolic enzymes was downregulated in the ASD group [18]. However, genetic mutations were not taken into consideration in our previous work.…”

Section: Discussionmentioning

confidence: 99%

“…FADS1/2 and ELOVL2 gene polymorphisms may be the primary determinants not only of LC-PUFA status, but also of the biological effects exerted by LC-PUFAs [9]. We previously reported that serum LC-PUFA levels and delta-6 and -5 desaturase and elongase 2 were downregulated in a rat model of ASD relative to control rats under the same dietary conditions [18]. These findings indicate that mutations in the FADS1/2 and ELOVL2 genes resulting in abnormal expression of delta-6 and -5 desaturase and elongase 2, possibly due to perturbed LC-PUFA status during critical stages of neural development that increases susceptibility to ASD.…”

Section: Introductionmentioning

confidence: 99%

FADS1-FADS2 and ELOVL2 gene polymorphisms in susceptibility to autism spectrum disorders in Chinese children

et al. 2018

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BackgroudAutism spectrum disorders (ASD) are a complex group of neurodevelopmental disorders with a genetic basis. The role of long-chain polyunsaturated fatty acids (LC-PUFAs) and the occurrence of autism has been the focus of many recent studies. The present study investigates whether genetic variants of the fatty acid desaturase (FADS) 1/2 and elongation of very long-chain fatty acids protein (ELOVL) 2 genes, which are involved in LC-PUFA metabolism, are associated with ASD risk.MethodsA cohort of 243 ASD patients and 243 unrelated healthy controls were enrolled in this case control study. Sixteen tag single nucleotide polymorphisms from the FADS1–2 and ELOVL2 genes were genotyped using the Sequenom Mass Array.ResultsThere were significant differences in allelic distribution of FADS2 rs526126 (OR = 0.55, 95% CI = 0.42–0.72, pFDR < 0.05) between autistic children and controls. FADS2 rs526126 and ELOVL2 rs10498676 were associated with decreased ASD risk in recessive model (OR = 0.07, 95% CI = 0.02–0.22, pFDR < 0.01; OR = 0.56, 95% CI = 0.35–0.89, pFDR = 0.042), while ELOVL2 rs17606561, rs3756963, and rs9468304 were associated with increased ASD risk in overdominant model (OR = 1.63, 95% CI = 1.12–2.36, pFDR = 0.036; OR = 1.64, 95% CI = 1.14–2.37, pFDR = 0.039; OR = 1.75, 95% CI = 1.22–2.50, pFDR = 0.017). The A/A genotype of rs10498676 was correlated with a decline in the Autism Diagnostic Interview-Revised communication (verbal and nonverbal) domain.ConclusionsThese findings provide evidence of an association between FADS2 and ELOVL2 polymorphisms and ASD susceptibility in Chinese children.Electronic supplementary materialThe online version of this article (10.1186/s12888-018-1868-7) contains supplementary material, which is available to authorized users.

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“…Moreover, the enhancement of eCB signal could promote the formation of LTD, and rescue the lack of eCB-mediated LTD in two types of monogenetic model of ASD mice [7]. Intriguingly, studies from our laboratory previously reported lower n-3 PUFAs levels were in autistic children, as well as in valproic acid (VPA)-induced rats [8,9], and the expressions of rate-limiting PUFA metabolic enzymes were downregulated in the VPA rats [8]. Afterwards, both prenatal and postnatal n-3 PUFA supplementation could markedly improve the learning and memory de cits of offspring [10].…”

Section: Introductionmentioning

confidence: 95%

The Alternations of Endocannabinoid System and its Therapeutic Potential in Autism Spectrum Disorder

Liu

Xie

Wang

et al. 2020

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Background: Autism spectrum disorder (ASD) is a group of developmental disabilities whose etiology remains elusive. The endocannabinoid (eCB) system modulated neurotransmission and neuronal plasticity. Evidence points to the involvement of this neuromodulatory system in the pathophysiology of ASD. Herein we investigated if there was disruption of eCB system in ASD and if pharmacological modulators of eCB system might have a therapeutic potential. Methods: We examined three major components of eCB system, namely, endogenous cannabinoids, their receptors and associated enzymes, in ASD children as well as in VPA-induced ASD animal model. Meanwhile we specially increased 2-arachidonylglycerol (2-AG) by administering JZL184, a selective inhibitor of monoacylglycerol lipase, the hydrolytic enzyme for 2-AG, and to examine ASD-like behaviors in VPA-induced rats. Results: Autistic children and VPA-induced rats exhibited the reduced eCBs content, elevated degrading enzymes, and up-regulation of CBRs. We found that repetitive and stereotypical behaviors, hyperactivity, sociability, social preference, and cognitive functioning were improved after acute and chronic JZL184 treatment. The major efficacy of JZL184 was observed at the dose of 3mg/kg for both affecting eCB system and ASD-like behaviors. Conclusions: There were a lower eCB signaling in autistic children and ASD animal model, and boosting 2-AG could ameliorate ASD-like phenotypes in animals. Collectively, the results suggest a novel approach to ASD treatment.

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Study of the serum levels of polyunsaturated fatty acids and the expression of related liver metabolic enzymes in a rat valproate‐induced autism model

Cited by 12 publications

References 34 publications

A Systematic Review of the Valproic-Acid-Induced Rodent Model of Autism

A Systematic Review of the Valproic-Acid-Induced Rodent Model of Autism

FADS1-FADS2 and ELOVL2 gene polymorphisms in susceptibility to autism spectrum disorders in Chinese children

The Alternations of Endocannabinoid System and its Therapeutic Potential in Autism Spectrum Disorder

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