Final published version
Licence: Other
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - Behavioral alterations in autism model induced by valproic acid and translational analysis of circulating microRNA
AU - Hirsch, Mauro Mozael
AU - Deckmann, Iohanna
AU - Fontes-Dutra, Mellanie
AU - Bauer-Negrini, Guilherme
AU - Della-Flora Nunes, Gustavo
AU - Nunes, Walquiria
AU - Rabelo, Bruna
AU - Riesgo, Rudimar
AU - Margis, Rogerio
AU - Bambini-Junior, Victorio
AU - Gottfried, Carmem
N1 - Copyright © 2018 Elsevier Ltd. All rights reserved.
PY - 2018/5/31
Y1 - 2018/5/31
N2 - 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.
AB - 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.
KW - Adolescent
KW - Animals
KW - Anticonvulsants/toxicity
KW - Antioxidants/pharmacology
KW - Autistic Disorder/chemically induced
KW - Behavior, Animal/drug effects
KW - Child
KW - Child, Preschool
KW - Circulating MicroRNA/blood
KW - Disease Models, Animal
KW - Female
KW - Humans
KW - Male
KW - Maternal Exposure
KW - MicroRNAs/blood
KW - Pregnancy
KW - Prenatal Exposure Delayed Effects
KW - Protein Biosynthesis
KW - Rats, Wistar
KW - Resveratrol
KW - Stilbenes/pharmacology
KW - Valproic Acid/toxicity
U2 - 10.1016/j.fct.2018.02.061
DO - 10.1016/j.fct.2018.02.061
M3 - Journal article
C2 - 29510222
VL - 115
SP - 336
EP - 343
JO - Food and Chemical Toxicology
JF - Food and Chemical Toxicology
SN - 0278-6915
ER -