Frontiers in Synaptic Neuroscience (May 2018)
Resveratrol Prevents Cellular and Behavioral Sensory Alterations in the Animal Model of Autism Induced by Valproic Acid
- Mellanie Fontes-Dutra,
- Mellanie Fontes-Dutra,
- Mellanie Fontes-Dutra,
- Júlio Santos-Terra,
- Júlio Santos-Terra,
- Júlio Santos-Terra,
- Iohanna Deckmann,
- Iohanna Deckmann,
- Iohanna Deckmann,
- Gustavo Brum Schwingel,
- Gustavo Brum Schwingel,
- Gustavo Brum Schwingel,
- Gustavo Della-Flora Nunes,
- Gustavo Della-Flora Nunes,
- Gustavo Della-Flora Nunes,
- Mauro Mozael Hirsch,
- Mauro Mozael Hirsch,
- Mauro Mozael Hirsch,
- Guilherme Bauer-Negrini,
- Guilherme Bauer-Negrini,
- Guilherme Bauer-Negrini,
- Rudimar S. Riesgo,
- Rudimar S. Riesgo,
- Rudimar S. Riesgo,
- Victorio Bambini-Júnior,
- Victorio Bambini-Júnior,
- Victorio Bambini-Júnior,
- Cecília Hedin-Pereira,
- Cecília Hedin-Pereira,
- Cecília Hedin-Pereira,
- Carmem Gottfried,
- Carmem Gottfried,
- Carmem Gottfried
Affiliations
- Mellanie Fontes-Dutra
- Translational Research Group in Autism Spectrum Disorders (GETTEA), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Mellanie Fontes-Dutra
- Department of Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Mellanie Fontes-Dutra
- National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
- Júlio Santos-Terra
- Translational Research Group in Autism Spectrum Disorders (GETTEA), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Júlio Santos-Terra
- Department of Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Júlio Santos-Terra
- National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
- Iohanna Deckmann
- Translational Research Group in Autism Spectrum Disorders (GETTEA), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Iohanna Deckmann
- Department of Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Iohanna Deckmann
- National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
- Gustavo Brum Schwingel
- Translational Research Group in Autism Spectrum Disorders (GETTEA), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Gustavo Brum Schwingel
- Department of Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Gustavo Brum Schwingel
- National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
- Gustavo Della-Flora Nunes
- Translational Research Group in Autism Spectrum Disorders (GETTEA), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Gustavo Della-Flora Nunes
- National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
- Gustavo Della-Flora Nunes
- Department of Biochemistry, University of Buffalo, The State University of New York, New York, NY, United States
- Mauro Mozael Hirsch
- Translational Research Group in Autism Spectrum Disorders (GETTEA), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Mauro Mozael Hirsch
- Department of Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Mauro Mozael Hirsch
- National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
- Guilherme Bauer-Negrini
- Translational Research Group in Autism Spectrum Disorders (GETTEA), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Guilherme Bauer-Negrini
- Department of Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Guilherme Bauer-Negrini
- National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
- Rudimar S. Riesgo
- Translational Research Group in Autism Spectrum Disorders (GETTEA), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Rudimar S. Riesgo
- National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
- Rudimar S. Riesgo
- Child Neurology Unit, Clinical Hospital of Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
- Victorio Bambini-Júnior
- Translational Research Group in Autism Spectrum Disorders (GETTEA), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Victorio Bambini-Júnior
- National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
- Victorio Bambini-Júnior
- School of Pharmacology and Biomedical Sciences, University of Central Lancashire, Preston, United Kingdom
- Cecília Hedin-Pereira
- National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
- Cecília Hedin-Pereira
- Institute of Biophysics Carlos Chagas Filho and Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
- Cecília Hedin-Pereira
- VPPCB, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil
- Carmem Gottfried
- Translational Research Group in Autism Spectrum Disorders (GETTEA), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Carmem Gottfried
- Department of Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Carmem Gottfried
- National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
- DOI
- https://doi.org/10.3389/fnsyn.2018.00009
- Journal volume & issue
-
Vol. 10
Abstract
Autism spectrum disorder (ASD) is characterized by impairments in both social communication and interaction and repetitive or stereotyped behaviors. Although its etiology remains unknown, genetic and environmental risk factors have been associated with this disorder, including the exposure to valproic acid (VPA) during pregnancy. Resveratrol (RSV) is an anti-inflammatory and antioxidant molecule known to prevent social impairments in the VPA animal model of autism. This study aimed to analyze the effects of prenatal exposure to VPA, as well as possible preventive effects of RSV, on sensory behavior, the localization of GABAergic parvalbumin (PV+) neurons in sensory brain regions and the expression of proteins of excitatory and inhibitory synapses. Pregnant rats were treated daily with RSV (3.6 mg/kg) from E6.5 to E18.5 and injected with VPA (600 mg/kg) in the E12.5. Male pups were analyzed in Nest Seeking (NS) behavior and in whisker nuisance task (WNT). At P30, the tissues were removed and analyzed by immunofluorescence and western blotting. Our data showed for the first time an altered localization of PV+-neurons in primary sensory cortex and amygdala. We also showed a reduced level of gephyrin in the primary somatosensory area (PSSA) of VPA animals. The treatment with RSV prevented all the aforementioned alterations triggered by VPA. Our data shed light on the relevance of sensory component in ASD and highlights the interplay between RSV and VPA animal model as an important tool to investigate the pathophysiology of ASD.
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