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2 recherche sur le mot-clé 'Valproic Acid/administration & dosage/toxicity'
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The valproic acid rat model of autism presents with gut bacterial dysbiosis similar to that in human autism / F. LIU in Molecular Autism, 9 (2018)
[article]
Titre : The valproic acid rat model of autism presents with gut bacterial dysbiosis similar to that in human autism Type de document : Texte imprimé et/ou numérique Auteurs : F. LIU, Auteur ; K. HORTON-SPARKS, Auteur ; V. HULL, Auteur ; R. W. LI, Auteur ; V. MARTINEZ-CERDENO, Auteur Article en page(s) : 61 p. Langues : Anglais (eng) Mots-clés : Animals Autistic Disorder/etiology/*microbiology Bacterial Typing Techniques Disease Models, Animal Dysbiosis/etiology/*microbiology *Gastrointestinal Microbiome Rats Rats, Sprague-Dawley Valproic Acid/administration & dosage/toxicity Index. décimale : PER Périodiques Résumé : Background: Gut microbiota has the capacity to impact the regular function of the brain, which can in turn affect the composition of microbiota. Autism spectrum disorder (ASD) patients suffer from gastrointestinal problems and experience changes in gut microbiota; however, it is not yet clear whether the change in the microbiota associated with ASD is a cause or a consequence of the disease. Methods: We have investigated the species richness and microbial composition in a valproic acid (VPA)-induced rat model autism. Fecal samples from the rectum were collected at necropsy, microbial total DNA was extracted, 16 rRNA genes sequenced using Illumina, and the global microbial co-occurrence network was constructed using a random matrix theory-based pipeline. Collected rat microbiome data were compared to available data derived from cases of autism. Results: We found that VPA administration during pregnancy reduced fecal microbial richness, changed the gut microbial composition, and altered the metabolite potential of the fecal microbial community in a pattern similar to that seen in patients with ASD. However, the global network property and network composition as well as microbial co-occurrence patterns were largely preserved in the offspring of rats exposed to prenatal administration of VPA. Conclusions: Our data on the microbiota of the VPA rat model of autism indicate that this model, in addition to behaviorally and anatomically mimicking the autistic brain as previously shown, also mimics the microbiome features of autism, making it one of the best-suited rodent models for the study of autism and ASD. En ligne : https://dx.doi.org/10.1186/s13229-018-0251-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389
in Molecular Autism > 9 (2018) . - 61 p.[article] The valproic acid rat model of autism presents with gut bacterial dysbiosis similar to that in human autism [Texte imprimé et/ou numérique] / F. LIU, Auteur ; K. HORTON-SPARKS, Auteur ; V. HULL, Auteur ; R. W. LI, Auteur ; V. MARTINEZ-CERDENO, Auteur . - 61 p.
Langues : Anglais (eng)
in Molecular Autism > 9 (2018) . - 61 p.
Mots-clés : Animals Autistic Disorder/etiology/*microbiology Bacterial Typing Techniques Disease Models, Animal Dysbiosis/etiology/*microbiology *Gastrointestinal Microbiome Rats Rats, Sprague-Dawley Valproic Acid/administration & dosage/toxicity Index. décimale : PER Périodiques Résumé : Background: Gut microbiota has the capacity to impact the regular function of the brain, which can in turn affect the composition of microbiota. Autism spectrum disorder (ASD) patients suffer from gastrointestinal problems and experience changes in gut microbiota; however, it is not yet clear whether the change in the microbiota associated with ASD is a cause or a consequence of the disease. Methods: We have investigated the species richness and microbial composition in a valproic acid (VPA)-induced rat model autism. Fecal samples from the rectum were collected at necropsy, microbial total DNA was extracted, 16 rRNA genes sequenced using Illumina, and the global microbial co-occurrence network was constructed using a random matrix theory-based pipeline. Collected rat microbiome data were compared to available data derived from cases of autism. Results: We found that VPA administration during pregnancy reduced fecal microbial richness, changed the gut microbial composition, and altered the metabolite potential of the fecal microbial community in a pattern similar to that seen in patients with ASD. However, the global network property and network composition as well as microbial co-occurrence patterns were largely preserved in the offspring of rats exposed to prenatal administration of VPA. Conclusions: Our data on the microbiota of the VPA rat model of autism indicate that this model, in addition to behaviorally and anatomically mimicking the autistic brain as previously shown, also mimics the microbiome features of autism, making it one of the best-suited rodent models for the study of autism and ASD. En ligne : https://dx.doi.org/10.1186/s13229-018-0251-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389 Sociability deficits after prenatal exposure to valproic acid are rescued by early social enrichment / M. CAMPOLONGO in Molecular Autism, 9 (2018)
[article]
Titre : Sociability deficits after prenatal exposure to valproic acid are rescued by early social enrichment Type de document : Texte imprimé et/ou numérique Auteurs : M. CAMPOLONGO, Auteur ; N. KAZLAUSKAS, Auteur ; G. FALASCO, Auteur ; L. URRUTIA, Auteur ; N. SALGUEIRO, Auteur ; C. HOCHT, Auteur ; Amaicha Mara DEPINO, Auteur Article en page(s) : 36p. Langues : Anglais (eng) Mots-clés : Animals Autism Spectrum Disorder/etiology/therapy Brain/diagnostic imaging Female Male Mice Pregnancy Prenatal Exposure Delayed Effects/drug therapy/etiology Social Behavior Socioenvironmental Therapy/methods Valproic Acid/administration & dosage/toxicity Autism spectrum disorder Dopamine Piriform cortex Sociability Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorder (ASD) is characterized by impaired social interactions and repetitive patterns of behavior. Symptoms appear in early life and persist throughout adulthood. Early social stimulation can help reverse some of the symptoms, but the biological mechanisms of these therapies are unknown. By analyzing the effects of early social stimulation on ASD-related behavior in the mouse, we aimed to identify brain structures that contribute to these behaviors. Methods: We injected pregnant mice with 600-mg/kg valproic acid (VPA) or saline (SAL) at gestational day 12.5 and evaluated the effect of weaning their offspring in cages containing only VPA animals, only SAL animals, or mixed. We analyzed juvenile play at PD21 and performed a battery of behavioral tests in adulthood. We then used preclinical PET imaging for an unbiased analysis of the whole brain of these mice and studied the function of the piriform cortex by c-Fos immunoreactivity and HPLC. Results: Compared to control animals, VPA-exposed animals play less as juveniles and exhibit a lower frequency of social interaction in adulthood when reared with other VPA mice. In addition, these animals were less likely to investigate social odors in the habituation/dishabituation olfactory test. However, when VPA animals were weaned with control animals, these behavioral alterations were not observed. Interestingly, repetitive behaviors and depression-related behaviors were not affected by social enrichment. We also found that VPA animals present high levels of glucose metabolism bilaterally in the piriform cortex (Pir), a region known to be involved in social behaviors. Moreover, we found alterations in the somatosensory, motor, and insular cortices. Remarkably, these effects were mostly reversed after social stimulation. To evaluate if changes in glucose metabolism in the Pir correlated with changes in neuronal activity, we measured c-Fos immunoreactivity in the Pir and found it increased in animals prenatally exposed to VPA. We further found increased dopamine turnover in the Pir. Both alterations were largely reversed by social enrichment. Conclusions: We show that early social enrichment can specifically rescue social deficits in a mouse model of ASD. Our results identified the Pir as a structure affected by VPA-exposure and social enrichment, suggesting that it could be a key component of the social brain circuitry. En ligne : https://dx.doi.org/10.1186/s13229-018-0221-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371
in Molecular Autism > 9 (2018) . - 36p.[article] Sociability deficits after prenatal exposure to valproic acid are rescued by early social enrichment [Texte imprimé et/ou numérique] / M. CAMPOLONGO, Auteur ; N. KAZLAUSKAS, Auteur ; G. FALASCO, Auteur ; L. URRUTIA, Auteur ; N. SALGUEIRO, Auteur ; C. HOCHT, Auteur ; Amaicha Mara DEPINO, Auteur . - 36p.
Langues : Anglais (eng)
in Molecular Autism > 9 (2018) . - 36p.
Mots-clés : Animals Autism Spectrum Disorder/etiology/therapy Brain/diagnostic imaging Female Male Mice Pregnancy Prenatal Exposure Delayed Effects/drug therapy/etiology Social Behavior Socioenvironmental Therapy/methods Valproic Acid/administration & dosage/toxicity Autism spectrum disorder Dopamine Piriform cortex Sociability Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorder (ASD) is characterized by impaired social interactions and repetitive patterns of behavior. Symptoms appear in early life and persist throughout adulthood. Early social stimulation can help reverse some of the symptoms, but the biological mechanisms of these therapies are unknown. By analyzing the effects of early social stimulation on ASD-related behavior in the mouse, we aimed to identify brain structures that contribute to these behaviors. Methods: We injected pregnant mice with 600-mg/kg valproic acid (VPA) or saline (SAL) at gestational day 12.5 and evaluated the effect of weaning their offspring in cages containing only VPA animals, only SAL animals, or mixed. We analyzed juvenile play at PD21 and performed a battery of behavioral tests in adulthood. We then used preclinical PET imaging for an unbiased analysis of the whole brain of these mice and studied the function of the piriform cortex by c-Fos immunoreactivity and HPLC. Results: Compared to control animals, VPA-exposed animals play less as juveniles and exhibit a lower frequency of social interaction in adulthood when reared with other VPA mice. In addition, these animals were less likely to investigate social odors in the habituation/dishabituation olfactory test. However, when VPA animals were weaned with control animals, these behavioral alterations were not observed. Interestingly, repetitive behaviors and depression-related behaviors were not affected by social enrichment. We also found that VPA animals present high levels of glucose metabolism bilaterally in the piriform cortex (Pir), a region known to be involved in social behaviors. Moreover, we found alterations in the somatosensory, motor, and insular cortices. Remarkably, these effects were mostly reversed after social stimulation. To evaluate if changes in glucose metabolism in the Pir correlated with changes in neuronal activity, we measured c-Fos immunoreactivity in the Pir and found it increased in animals prenatally exposed to VPA. We further found increased dopamine turnover in the Pir. Both alterations were largely reversed by social enrichment. Conclusions: We show that early social enrichment can specifically rescue social deficits in a mouse model of ASD. Our results identified the Pir as a structure affected by VPA-exposure and social enrichment, suggesting that it could be a key component of the social brain circuitry. En ligne : https://dx.doi.org/10.1186/s13229-018-0221-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371