Behavioral alterations in autism model induced by valproic acid and translational analysis of circulating microRNA

被引：48

作者：

Hirsch, Mauro Mozael ^{[1
,2
,3
]}

Declunann, Iohanna ^{[1
,2
,3
]}

Fontes-Dutra, Mellanie ^{[1
,2
,5
,6
]}

Bauer-Negrini, Guilherme ^{[1
,2
,3
]}

Nunes, Gustavo Della-Flora ^{[1
,2
,3
]}

Nunes, Walquiria ^{[1
,2
,3
]}

Rabelo, Bruna ^{[1
,2
]}

Riesgo, Rudimar ^{[1
,3
,4
]}

Margis, Rogerio ^{[3
,5
,6
]}

Bambini-Junior, Victorio ^{[1
,3
,7
]}

Gottfried, Carmem ^{[1
,2
,3
]}

机构：

[1] Clin Hosp Porto Alegre, Translat Grp Autism Spectrum Disorder GETTEA, Porto Alegre, RS, Brazil

[2] Fed Univ Rio Grande Do Sul UFRGS, Dept Biochem, Porto Alegre, RS, Brazil

[3] Brazilian Natl Inst Sci & Technol Neuroimmunomodu, Rio De Janeiro, Brazil

[4] Univ Fed Rio Grande do Sul, Clin Hosp Porto Alegre, Child Neurol Unit, Porto Alegre, RS, Brazil

[5] Fed Univ Rio Grande Do Sul UFRGS, Ctr Biotechnol, Porto Alegre, RS, Brazil

[6] Fed Univ Rio Grande Do Sul UFRGS, PPGBCM, Lab Genomes & Plant Populat, Porto Alegre, RS, Brazil

[7] Univ Cent Lancashire, Sch Pharm & Biomed Sci, Preston, Lancs, England

来源：

FOOD AND CHEMICAL TOXICOLOGY | 2018年 / 115卷

关键词：

ASD; microRNA; Resveratrol; Translational research; Social behavior; Valproate; SPECTRUM DISORDER; ANIMAL-MODEL; SOCIAL TRANSMISSION; PRENATAL EXPOSURE; FOOD PREFERENCE; RT-PCR; EXPRESSION; RATS; ASSOCIATION; BIOMARKERS;

D O I：

10.1016/j.fct.2018.02.061

中图分类号：

TS2 [食品工业];

学科分类号：

0832 ;

摘要：

Autism spectrum disorder (ASD) is characterized by difficulties in social interaction, communication and language, and restricted repertoire of activities and interests. The etiology of ASD remains unknown and no clinical markers for diagnosis were identified. Environmental factors, including prenatal exposure to valproic acid (VPA), may contribute to increased risk of developing ASD. MicroRNA (miRNA) are small noncoding RNA that regulate gene expression and are frequently linked to biological processes affected in neurodevelopmental disorders. In this work, we analyzed the effects of resveratrol (an antioxidant and anti-inflammatory molecule) on behavioral alterations of the VPA model of autism, as well as the levels of circulating miRNA. We also evaluated the same set of miRNA in autistic patients. Rats of the VPA model of autism showed reduced total reciprocal social interaction, prevented by prenatal treatment with resveratrol (RSV). The levels of miR134-5p and miR138-5p increased in autistic patients. Interestingly, miR134-5p is also upregulated in animals of the VPA model, which is prevented by RSV. In conclusion, our findings revealed important preventive actions of RSV in the VPA model, ranging from behavior to molecular alterations. Further evaluation of preventive mechanisms of RSV can shed light in important biomarkers and etiological triggers of ASD.

引用

页码：336 / 343

页数：8

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