Improvement by methylphenidate and atomoxetine of social interaction deficits and recognition memory impairment in a mouse model of valproic acid-induced autism / Yuta HARA in Autism Research, 9-9 (September 2016)  

Public ISBD [article]  inAutism Research > 9-9 (September 2016) . - p.926-939 Titre : Improvement by methylphenidate and atomoxetine of social interaction deficits and recognition memory impairment in a mouse model of valproic acid-induced autism Type de document : Texte imprimé et/ou numérique Auteurs : Yuta HARA, Auteur ; Yukio AGO, Auteur ; Atsuki TARUTA, Auteur ; Keisuke KATASHIBA, Auteur ; Shigeru HASEBE, Auteur ; Erika TAKANO, Auteur ; Yusuke ONAKA, Auteur ; Hitoshi HASHIMOTO, Auteur ; Toshio MATSUDA, Auteur ; Kazuhiro TAKUMA, Auteur Article en page(s) : p.926-939 Langues : Anglais (eng) Mots-clés : valproic acid  methylphenidate  atomoxetine  behavioral analysis  animal model Index. décimale : PER Périodiques Résumé : Rodents exposed prenatally to valproic acid (VPA) show autism-related behavioral abnormalities. We recently found that prenatal VPA exposure causes a reduction of dopaminergic activity in the prefrontal cortex of male, but not female, mice. This suggests that reduced prefrontal dopaminergic activity is associated with behavioral abnormalities in VPA-treated mice. In the present study, we examined whether the attention deficit/hyperactivity disorder drugs methylphenidate and atomoxetine (which increase dopamine release in the prefrontal cortex, but not striatum, in mice) could alleviate the behavioral abnormalities and changes in dendritic spine morphology induced by prenatal VPA exposure. We found that methylphenidate and atomoxetine increased prefrontal dopamine and noradrenaline release in VPA-treated mice. Acute treatment with methylphenidate or atomoxetine did not alleviate the social interaction deficits or recognition memory impairment in VPA-treated mice, while chronic treatment for 2 weeks did. Methylphenidate or atomoxetine for 2 weeks also improved the prenatal VPA-induced decrease in dendritic spine density in the prefrontal cortex. The effects of these drugs on behaviors and dendritic spine morphology were antagonized by concomitant treatment with the dopamine-D1 receptor antagonist SCH39166 or the dopamine-D2 receptor antagonist raclopride, but not by the ?2-adrenoceptor antagonist idazoxan. These findings suggest that chronic treatment with methylphenidate or atomoxetine improves abnormal behaviors and diminishes the reduction in spine density in VPA-treated mice via a prefrontal dopaminergic system-dependent mechanism. En ligne : http://dx.doi.org/10.1002/aur.1596 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=294 [article] Improvement by methylphenidate and atomoxetine of social interaction deficits and recognition memory impairment in a mouse model of valproic acid-induced autism [Texte imprimé et/ou numérique] / Yuta HARA, Auteur ; Yukio AGO, Auteur ; Atsuki TARUTA, Auteur ; Keisuke KATASHIBA, Auteur ; Shigeru HASEBE, Auteur ; Erika TAKANO, Auteur ; Yusuke ONAKA, Auteur ; Hitoshi HASHIMOTO, Auteur ; Toshio MATSUDA, Auteur ; Kazuhiro TAKUMA, Auteur . - p.926-939. Langues : Anglais (eng) in Autism Research > 9-9 (September 2016) . - p.926-939 Mots-clés : valproic acid  methylphenidate  atomoxetine  behavioral analysis  animal model Index. décimale : PER Périodiques Résumé : Rodents exposed prenatally to valproic acid (VPA) show autism-related behavioral abnormalities. We recently found that prenatal VPA exposure causes a reduction of dopaminergic activity in the prefrontal cortex of male, but not female, mice. This suggests that reduced prefrontal dopaminergic activity is associated with behavioral abnormalities in VPA-treated mice. In the present study, we examined whether the attention deficit/hyperactivity disorder drugs methylphenidate and atomoxetine (which increase dopamine release in the prefrontal cortex, but not striatum, in mice) could alleviate the behavioral abnormalities and changes in dendritic spine morphology induced by prenatal VPA exposure. We found that methylphenidate and atomoxetine increased prefrontal dopamine and noradrenaline release in VPA-treated mice. Acute treatment with methylphenidate or atomoxetine did not alleviate the social interaction deficits or recognition memory impairment in VPA-treated mice, while chronic treatment for 2 weeks did. Methylphenidate or atomoxetine for 2 weeks also improved the prenatal VPA-induced decrease in dendritic spine density in the prefrontal cortex. The effects of these drugs on behaviors and dendritic spine morphology were antagonized by concomitant treatment with the dopamine-D1 receptor antagonist SCH39166 or the dopamine-D2 receptor antagonist raclopride, but not by the ?2-adrenoceptor antagonist idazoxan. These findings suggest that chronic treatment with methylphenidate or atomoxetine improves abnormal behaviors and diminishes the reduction in spine density in VPA-treated mice via a prefrontal dopaminergic system-dependent mechanism. En ligne : http://dx.doi.org/10.1002/aur.1596 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=294

Prenatal exposure to valproic acid increases miR-132 levels in the mouse embryonic brain / Y. HARA in Molecular Autism, 8 (2017)  

Public ISBD [article]  inMolecular Autism > 8 (2017) . - 33p. Titre : Prenatal exposure to valproic acid increases miR-132 levels in the mouse embryonic brain Type de document : Texte imprimé et/ou numérique Auteurs : Y. HARA, Auteur ; Yukio AGO, Auteur ; E. TAKANO, Auteur ; S. HASEBE, Auteur ; T. NAKAZAWA, Auteur ; H. HASHIMOTO, Auteur ; T. MATSUDA, Auteur ; K. TAKUMA, Auteur Article en page(s) : 33p. Langues : Anglais (eng) Mots-clés : Autism mouse model  Embryonic brain  MicroRNA  Valproic acid Index. décimale : PER Périodiques Résumé : BACKGROUND: MicroRNAs, small non-coding RNAs, are highly expressed in the mammalian brain, and the dysregulation of microRNA levels may be involved in neurodevelopmental disorders such as autism spectrum disorder (ASD). In the present study, we examined whether prenatal valproic acid (VPA) exposure affects levels of microRNAs, especially the brain specific and enriched microRNAs, in the mouse embryonic brain. RESULTS: Prenatal exposure to VPA at E12.5 immediately increased miR-132 levels, but not miR-9 or miR-124 levels, in the male embryonic brain. Prenatal exposure to VPA at E12.5 also increased miR-132 levels in the female embryonic brain. We further found that the prenatal exposure to VPA at E12.5 increased mRNA levels of Arc, c-Fos and brain-derived neurotrophic factor in both male and female embryonic brains, prior to miR-132 expression. In contrast, prenatal exposure to VPA at E14.5 did not affect miR-132 levels in either male or female embryonic brain. The prenatal VPA exposure at E12.5 also decreased mRNA levels of methyl-CpG-binding protein 2 and Rho GTPase-activating protein p250GAP, both of which are molecular targets of miR-132. Furthermore, RNA sequence analysis revealed that prenatal VPA exposure caused changes in several microRNA levels other than miR-132 in the embryonic whole brain. CONCLUSIONS: These findings suggest that the alterations in neuronal activity-dependent microRNAs levels, including an increased level of miR-132, in the embryonic period, at least in part, underlie the ASD-like behaviors and cortical pathology produced by prenatal VPA exposure. En ligne : http://dx.doi.org/10.1186/s13229-017-0149-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330 [article] Prenatal exposure to valproic acid increases miR-132 levels in the mouse embryonic brain [Texte imprimé et/ou numérique] / Y. HARA, Auteur ; Yukio AGO, Auteur ; E. TAKANO, Auteur ; S. HASEBE, Auteur ; T. NAKAZAWA, Auteur ; H. HASHIMOTO, Auteur ; T. MATSUDA, Auteur ; K. TAKUMA, Auteur . - 33p. Langues : Anglais (eng) in Molecular Autism > 8 (2017) . - 33p. Mots-clés : Autism mouse model  Embryonic brain  MicroRNA  Valproic acid Index. décimale : PER Périodiques Résumé : BACKGROUND: MicroRNAs, small non-coding RNAs, are highly expressed in the mammalian brain, and the dysregulation of microRNA levels may be involved in neurodevelopmental disorders such as autism spectrum disorder (ASD). In the present study, we examined whether prenatal valproic acid (VPA) exposure affects levels of microRNAs, especially the brain specific and enriched microRNAs, in the mouse embryonic brain. RESULTS: Prenatal exposure to VPA at E12.5 immediately increased miR-132 levels, but not miR-9 or miR-124 levels, in the male embryonic brain. Prenatal exposure to VPA at E12.5 also increased miR-132 levels in the female embryonic brain. We further found that the prenatal exposure to VPA at E12.5 increased mRNA levels of Arc, c-Fos and brain-derived neurotrophic factor in both male and female embryonic brains, prior to miR-132 expression. In contrast, prenatal exposure to VPA at E14.5 did not affect miR-132 levels in either male or female embryonic brain. The prenatal VPA exposure at E12.5 also decreased mRNA levels of methyl-CpG-binding protein 2 and Rho GTPase-activating protein p250GAP, both of which are molecular targets of miR-132. Furthermore, RNA sequence analysis revealed that prenatal VPA exposure caused changes in several microRNA levels other than miR-132 in the embryonic whole brain. CONCLUSIONS: These findings suggest that the alterations in neuronal activity-dependent microRNAs levels, including an increased level of miR-132, in the embryonic period, at least in part, underlie the ASD-like behaviors and cortical pathology produced by prenatal VPA exposure. En ligne : http://dx.doi.org/10.1186/s13229-017-0149-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330

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