14 recherche sur le mot-clé 'animal model'

Assessment of medical morbidities in a rhesus monkey model of naturally occurring low sociality / A. K. MYERS in Autism Research, 14-7 (July 2021)  

Public ISBD [article]  inAutism Research > 14-7 (July 2021) . - p.1332-1346 Titre : Assessment of medical morbidities in a rhesus monkey model of naturally occurring low sociality Type de document : Texte imprimé et/ou numérique Auteurs : A. K. MYERS, Auteur ; Catherine F. TALBOT, Auteur ; L. A. DEL ROSSO, Auteur ; A. C. MANESS, Auteur ; S. M. V. SIMMONS, Auteur ; J. P. GARNER, Auteur ; John P. CAPITANIO, Auteur ; Karen J. PARKER, Auteur Article en page(s) : p.1332-1346 Langues : Anglais (eng) Mots-clés : Animals  Autism Spectrum Disorder/epidemiology  Autistic Disorder  Humans  Macaca mulatta  Morbidity  Social Behavior  Social Responsiveness Scale  animal model  autism spectrum disorder  medical morbidities  rhesus macaque  social behavior Index. décimale : PER Périodiques Résumé : People with autism spectrum disorder (ASD) exhibit a variety of medical morbidities at significantly higher rates than the general population. Using an established monkey model of naturally occurring low sociality, we investigated whether low-social monkeys show an increased burden of medical morbidities compared to their high-social counterparts. We systematically reviewed the medical records of N = 152 (n = 73 low-social; n = 79 high-social) rhesus macaques (Macaca mulatta) to assess the number of traumatic injury, gastrointestinal, and inflammatory events, as well as the presence of rare medical conditions. Subjects' nonsocial scores, determined by the frequency they were observed in a nonsocial state (i.e., alone), and macaque Social Responsiveness Scale-Revised (mSRS-R) scores were also used to test whether individual differences in social functioning were related to medical morbidity burden. Medical morbidity type significantly differed by group, such that low-social monkeys incurred higher rates of traumatic injury compared to high-social monkeys. Nonsocial scores and mSRS-R scores also significantly and positively predicted traumatic injury rates, indicating that monkeys with the greatest social impairment were most impacted on this health measure. These findings from low-social monkeys are consistent with well-documented evidence that people with ASD incur a greater number of traumatic injuries and receive more peer bullying than their neurotypical peers, and add to growing evidence for the face validity of this primate model. LAY SUMMARY: People with autism exhibit multiple medical problems at higher rates than the general population. We conducted a comprehensive medical record review of monkeys that naturally exhibit differences in sociality and found that low-social monkeys are more susceptible to traumatic injuries than high-social monkeys. These results are consistent with reports that people with autism also incur greater traumatic injury and peer bullying and add to growing evidence for the validity of this monkey model. En ligne : http://dx.doi.org/10.1002/aur.2512 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=449 [article] Assessment of medical morbidities in a rhesus monkey model of naturally occurring low sociality [Texte imprimé et/ou numérique] / A. K. MYERS, Auteur ; Catherine F. TALBOT, Auteur ; L. A. DEL ROSSO, Auteur ; A. C. MANESS, Auteur ; S. M. V. SIMMONS, Auteur ; J. P. GARNER, Auteur ; John P. CAPITANIO, Auteur ; Karen J. PARKER, Auteur . - p.1332-1346. Langues : Anglais (eng) in Autism Research > 14-7 (July 2021) . - p.1332-1346 Mots-clés : Animals  Autism Spectrum Disorder/epidemiology  Autistic Disorder  Humans  Macaca mulatta  Morbidity  Social Behavior  Social Responsiveness Scale  animal model  autism spectrum disorder  medical morbidities  rhesus macaque  social behavior Index. décimale : PER Périodiques Résumé : People with autism spectrum disorder (ASD) exhibit a variety of medical morbidities at significantly higher rates than the general population. Using an established monkey model of naturally occurring low sociality, we investigated whether low-social monkeys show an increased burden of medical morbidities compared to their high-social counterparts. We systematically reviewed the medical records of N = 152 (n = 73 low-social; n = 79 high-social) rhesus macaques (Macaca mulatta) to assess the number of traumatic injury, gastrointestinal, and inflammatory events, as well as the presence of rare medical conditions. Subjects' nonsocial scores, determined by the frequency they were observed in a nonsocial state (i.e., alone), and macaque Social Responsiveness Scale-Revised (mSRS-R) scores were also used to test whether individual differences in social functioning were related to medical morbidity burden. Medical morbidity type significantly differed by group, such that low-social monkeys incurred higher rates of traumatic injury compared to high-social monkeys. Nonsocial scores and mSRS-R scores also significantly and positively predicted traumatic injury rates, indicating that monkeys with the greatest social impairment were most impacted on this health measure. These findings from low-social monkeys are consistent with well-documented evidence that people with ASD incur a greater number of traumatic injuries and receive more peer bullying than their neurotypical peers, and add to growing evidence for the face validity of this primate model. LAY SUMMARY: People with autism exhibit multiple medical problems at higher rates than the general population. We conducted a comprehensive medical record review of monkeys that naturally exhibit differences in sociality and found that low-social monkeys are more susceptible to traumatic injuries than high-social monkeys. These results are consistent with reports that people with autism also incur greater traumatic injury and peer bullying and add to growing evidence for the validity of this monkey model. En ligne : http://dx.doi.org/10.1002/aur.2512 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=449

A brain proteomic investigation of rapamycin effects in the Tsc1(+/-) mouse model / H. WESSELING in Molecular Autism, 8 (2017)  

Public ISBD [article]  inMolecular Autism > 8 (2017) . - 41p. Titre : A brain proteomic investigation of rapamycin effects in the Tsc1(+/-) mouse model Type de document : Texte imprimé et/ou numérique Auteurs : H. WESSELING, Auteur ; Y. ELGERSMA, Auteur ; S. BAHN, Auteur Article en page(s) : 41p. Langues : Anglais (eng) Mots-clés : Animal model  Proteomics  Rapamycin  Srm  Tuberous sclerosis Index. décimale : PER Périodiques Résumé : BACKGROUND: Tuberous sclerosis complex (TSC) is a rare monogenic disorder characterized by benign tumors in multiple organs as well as a high prevalence of epilepsy, intellectual disability and autism. TSC is caused by inactivating mutations in the TSC1 or TSC2 genes. Heterozygocity induces hyperactivation of mTOR which can be inhibited by mTOR inhibitors, such as rapamycin, which have proven efficacy in the treatment of TSC-associated symptoms. The aim of the present study was (1) to identify molecular changes associated with social and cognitive deficits in the brain tissue of Tsc1(+/-) mice and (2) to investigate the molecular effects of rapamycin treatment, which has been shown to ameliorate genotype-related behavioural deficits. METHODS: Molecular alterations in the frontal cortex and hippocampus of Tsc1(+/-) and control mice, with or without rapamycin treatment, were investigated. A quantitative mass spectrometry-based shotgun proteomic approach (LC-MS(E)) was employed as an unbiased method to detect changes in protein levels. Changes identified in the initial profiling stage were validated using selected reaction monitoring (SRM). Protein Set Enrichment Analysis was employed to identify dysregulated pathways. RESULTS: LC-MS(E) analysis of Tsc1(+/-) mice and controls (n = 30) identified 51 proteins changed in frontal cortex and 108 in the hippocampus. Bioinformatic analysis combined with targeted proteomic validation revealed several dysregulated molecular pathways. Using targeted assays, proteomic alterations in the hippocampus validated the pathways "myelination", "dendrite," and "oxidative stress", an upregulation of ribosomal proteins and the mTOR kinase. LC-MS(E) analysis was also employed on Tsc1(+/-) and wildtype mice (n = 34) treated with rapamycin or vehicle. Rapamycin treatment exerted a stronger proteomic effect in Tsc1(+/-) mice with significant changes (mainly decreased expression) in 231 and 106 proteins, respectively. The cellular pathways "oxidative stress" and "apoptosis" were found to be affected in Tsc1(+/-) mice and the cellular compartments "myelin sheet" and "neurofilaments" were affected by rapamycin treatment. Thirty-three proteins which were altered in Tsc1(+/-) mice were normalized following rapamycin treatment, amongst them oxidative stress related proteins, myelin-specific and ribosomal proteins. CONCLUSIONS: Molecular changes in the Tsc1(+/-) mouse brain were more prominent in the hippocampus compared to the frontal cortex. Pathways linked to myelination and oxidative stress response were prominently affected and, at least in part, normalized following rapamycin treatment. The results could aid in the identification of novel drug targets for the treatment of cognitive, social and psychiatric symptoms in autism spectrum disorders. Similar pathways have also been implicated in other psychiatric and neurodegenerative disorders and could imply similar disease processes. Thus, the potential efficacy of mTOR inhibitors warrants further investigation not only for autism spectrum disorders but also for other neuropsychiatric and neurodegenerative diseases. En ligne : http://dx.doi.org/10.1186/s13229-017-0151-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=331 [article] A brain proteomic investigation of rapamycin effects in the Tsc1(+/-) mouse model [Texte imprimé et/ou numérique] / H. WESSELING, Auteur ; Y. ELGERSMA, Auteur ; S. BAHN, Auteur . - 41p. Langues : Anglais (eng) in Molecular Autism > 8 (2017) . - 41p. Mots-clés : Animal model  Proteomics  Rapamycin  Srm  Tuberous sclerosis Index. décimale : PER Périodiques Résumé : BACKGROUND: Tuberous sclerosis complex (TSC) is a rare monogenic disorder characterized by benign tumors in multiple organs as well as a high prevalence of epilepsy, intellectual disability and autism. TSC is caused by inactivating mutations in the TSC1 or TSC2 genes. Heterozygocity induces hyperactivation of mTOR which can be inhibited by mTOR inhibitors, such as rapamycin, which have proven efficacy in the treatment of TSC-associated symptoms. The aim of the present study was (1) to identify molecular changes associated with social and cognitive deficits in the brain tissue of Tsc1(+/-) mice and (2) to investigate the molecular effects of rapamycin treatment, which has been shown to ameliorate genotype-related behavioural deficits. METHODS: Molecular alterations in the frontal cortex and hippocampus of Tsc1(+/-) and control mice, with or without rapamycin treatment, were investigated. A quantitative mass spectrometry-based shotgun proteomic approach (LC-MS(E)) was employed as an unbiased method to detect changes in protein levels. Changes identified in the initial profiling stage were validated using selected reaction monitoring (SRM). Protein Set Enrichment Analysis was employed to identify dysregulated pathways. RESULTS: LC-MS(E) analysis of Tsc1(+/-) mice and controls (n = 30) identified 51 proteins changed in frontal cortex and 108 in the hippocampus. Bioinformatic analysis combined with targeted proteomic validation revealed several dysregulated molecular pathways. Using targeted assays, proteomic alterations in the hippocampus validated the pathways "myelination", "dendrite," and "oxidative stress", an upregulation of ribosomal proteins and the mTOR kinase. LC-MS(E) analysis was also employed on Tsc1(+/-) and wildtype mice (n = 34) treated with rapamycin or vehicle. Rapamycin treatment exerted a stronger proteomic effect in Tsc1(+/-) mice with significant changes (mainly decreased expression) in 231 and 106 proteins, respectively. The cellular pathways "oxidative stress" and "apoptosis" were found to be affected in Tsc1(+/-) mice and the cellular compartments "myelin sheet" and "neurofilaments" were affected by rapamycin treatment. Thirty-three proteins which were altered in Tsc1(+/-) mice were normalized following rapamycin treatment, amongst them oxidative stress related proteins, myelin-specific and ribosomal proteins. CONCLUSIONS: Molecular changes in the Tsc1(+/-) mouse brain were more prominent in the hippocampus compared to the frontal cortex. Pathways linked to myelination and oxidative stress response were prominently affected and, at least in part, normalized following rapamycin treatment. The results could aid in the identification of novel drug targets for the treatment of cognitive, social and psychiatric symptoms in autism spectrum disorders. Similar pathways have also been implicated in other psychiatric and neurodegenerative disorders and could imply similar disease processes. Thus, the potential efficacy of mTOR inhibitors warrants further investigation not only for autism spectrum disorders but also for other neuropsychiatric and neurodegenerative diseases. En ligne : http://dx.doi.org/10.1186/s13229-017-0151-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=331

Developmental social communication deficits in the Shank3 rat model of phelan-mcdermid syndrome and autism spectrum disorder / Elizabeth L. BERG in Autism Research, 11-4 (April 2018)  

Public ISBD [article]  inAutism Research > 11-4 (April 2018) . - p.587-601 Titre : Developmental social communication deficits in the Shank3 rat model of phelan-mcdermid syndrome and autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Elizabeth L. BERG, Auteur ; N. A. COPPING, Auteur ; J. K. RIVERA, Auteur ; M. C. PRIDE, Auteur ; Milo CAREAGA, Auteur ; M. D. BAUMAN, Auteur ; Robert F. BERMAN, Auteur ; P. J. LEIN, Auteur ; Hala HARONY-NICOLAS, Auteur ; Joseph D. BUXBAUM, Auteur ; J. ELLEGOOD, Auteur ; J. P. LERCH, Auteur ; M. WOHR, Auteur ; J. L. SILVERMAN, Auteur Article en page(s) : p.587-601 Langues : Anglais (eng) Mots-clés : Phelan McDermid Syndrome  animal model  autism  behavior  neurodevelopment  shank  social  synapse Index. décimale : PER Périodiques Résumé : Mutations in the SHANK3 gene have been discovered in autism spectrum disorder (ASD), and the intellectual disability, Phelan-McDermid Syndrome. This study leveraged a new rat model of Shank3 deficiency to assess complex behavioral phenomena, unique to rats, which display a richer social behavior repertoire than mice. Uniquely detectable emissions of ultrasonic vocalizations (USV) in rats serve as situation-dependent affective signals and accomplish important communicative functions. We report, for the first time, a call and response acoustic playback assay of bidirectional social communication in juvenile Shank3 rats. Interestingly, we found that Shank3-deficient null males did not demonstrate the enhanced social approach behavior typically exhibited following playback of pro-social USV. Concomitantly, we discovered that emission of USV in response to playback was not genotype-dependent and emitted response calls were divergent in meaning. This is the first report of these socially relevant responses using a genetic model of ASD. A comprehensive and empirical analysis of vigorous play during juvenile reciprocal social interactions further revealed fewer bouts and reduced durations of time spent playing by multiple key parameters, including reduced anogenital sniffing and allogrooming. We further discovered that male null Shank3-deficient pups emitted fewer isolation-induced USV than Shank3 wildtype controls. Postnatal whole brain anatomical phenotyping was applied to visualize anatomical substrates that underlie developmental phenotypes. The data presented here lend support for the important role of Shank3 in social communication, the core symptom domain of ASD. By increasing the number of in vivo functional outcome measures, we improved the likelihood for identifying and moving forward with medical interventions. Autism Res 2018, 11: 587-601. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Clinically relevant outcomes are required to demonstrate the utility of therapeutics. We introduce findings in a rat model, and assess the impact of mutations in Shank3, an autism risk gene. We found that males with deficient expression of Shank3 did not demonstrate typical responses in a bi-directional social communication test and that social interaction was lower on key parameters. Outcome measures reported herein extend earlier results in mice and capture responses to acoustic calls, which is analogous to measuring receptive and expressive communication. En ligne : http://dx.doi.org/10.1002/aur.1925 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=358 [article] Developmental social communication deficits in the Shank3 rat model of phelan-mcdermid syndrome and autism spectrum disorder [Texte imprimé et/ou numérique] / Elizabeth L. BERG, Auteur ; N. A. COPPING, Auteur ; J. K. RIVERA, Auteur ; M. C. PRIDE, Auteur ; Milo CAREAGA, Auteur ; M. D. BAUMAN, Auteur ; Robert F. BERMAN, Auteur ; P. J. LEIN, Auteur ; Hala HARONY-NICOLAS, Auteur ; Joseph D. BUXBAUM, Auteur ; J. ELLEGOOD, Auteur ; J. P. LERCH, Auteur ; M. WOHR, Auteur ; J. L. SILVERMAN, Auteur . - p.587-601. Langues : Anglais (eng) in Autism Research > 11-4 (April 2018) . - p.587-601 Mots-clés : Phelan McDermid Syndrome  animal model  autism  behavior  neurodevelopment  shank  social  synapse Index. décimale : PER Périodiques Résumé : Mutations in the SHANK3 gene have been discovered in autism spectrum disorder (ASD), and the intellectual disability, Phelan-McDermid Syndrome. This study leveraged a new rat model of Shank3 deficiency to assess complex behavioral phenomena, unique to rats, which display a richer social behavior repertoire than mice. Uniquely detectable emissions of ultrasonic vocalizations (USV) in rats serve as situation-dependent affective signals and accomplish important communicative functions. We report, for the first time, a call and response acoustic playback assay of bidirectional social communication in juvenile Shank3 rats. Interestingly, we found that Shank3-deficient null males did not demonstrate the enhanced social approach behavior typically exhibited following playback of pro-social USV. Concomitantly, we discovered that emission of USV in response to playback was not genotype-dependent and emitted response calls were divergent in meaning. This is the first report of these socially relevant responses using a genetic model of ASD. A comprehensive and empirical analysis of vigorous play during juvenile reciprocal social interactions further revealed fewer bouts and reduced durations of time spent playing by multiple key parameters, including reduced anogenital sniffing and allogrooming. We further discovered that male null Shank3-deficient pups emitted fewer isolation-induced USV than Shank3 wildtype controls. Postnatal whole brain anatomical phenotyping was applied to visualize anatomical substrates that underlie developmental phenotypes. The data presented here lend support for the important role of Shank3 in social communication, the core symptom domain of ASD. By increasing the number of in vivo functional outcome measures, we improved the likelihood for identifying and moving forward with medical interventions. Autism Res 2018, 11: 587-601. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Clinically relevant outcomes are required to demonstrate the utility of therapeutics. We introduce findings in a rat model, and assess the impact of mutations in Shank3, an autism risk gene. We found that males with deficient expression of Shank3 did not demonstrate typical responses in a bi-directional social communication test and that social interaction was lower on key parameters. Outcome measures reported herein extend earlier results in mice and capture responses to acoustic calls, which is analogous to measuring receptive and expressive communication. En ligne : http://dx.doi.org/10.1002/aur.1925 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=358

Early communication deficits in the Shank1 knockout mouse model for autism spectrum disorder: Developmental aspects and effects of social context / A. Özge SUNGUR in Autism Research, 9-6 (June 2016)  

Public ISBD [article]  inAutism Research > 9-6 (June 2016) . - p.696-709 Titre : Early communication deficits in the Shank1 knockout mouse model for autism spectrum disorder: Developmental aspects and effects of social context Type de document : Texte imprimé et/ou numérique Auteurs : A. Özge SUNGUR, Auteur ; Rainer K. W. SCHWARTING, Auteur ; Markus WÖHR, Auteur Article en page(s) : p.696-709 Langues : Anglais (eng) Mots-clés : animal model  postsynaptic density  neurodevelopmental disorders  autism  communication  ultrasonic vocalization  social context Index. décimale : PER Périodiques Résumé : Alterations in SHANK genes were repeatedly reported in autism spectrum disorder (ASD). ASD is a group of neurodevelopmental disorders diagnosed by persistent deficits in social communication/interaction across multiple contexts, with restricted/repetitive patterns of behavior. To date, diagnostic criteria for ASD are purely behaviorally defined and reliable biomarkers have still not been identified. The validity of mouse models for ASD therefore strongly relies on their behavioral phenotype. Here, we studied communication by means of isolation-induced pup ultrasonic vocalizations (USV) in the Shank1 mouse model for ASD by comparing Shank1?/? null mutant, Shank1+/? heterozygous, and Shank1+/+ wildtype littermate controls. The first aim of the present study was to evaluate the effects of Shank1 deletions on developmental aspects of communication in order to see whether ASD-related communication deficits are due to general impairment or delay in development. Second, we focused on social context effects on USV production. We show that Shank1?/? pups vocalized less and displayed a delay in the typical inverted U-shaped developmental USV emission pattern with USV rates peaking on postnatal day (PND) 9, resulting in a prominent genotype difference on PND6. Moreover, testing under social conditions revealed even more prominently genotype-dependent deficits regardless of the familiarity of the social context. As communication by definition serves a social function, introducing a social component to the typically nonsocial test environment could therefore help to reveal communication deficits in mouse models for ASD. Together, these results indicate that SHANK1 is involved in acoustic communication across species, with genetic alterations in SHANK1 resulting in social communication/interaction deficits. Autism Res 2016, 9: 696–709. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.1564 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=290 [article] Early communication deficits in the Shank1 knockout mouse model for autism spectrum disorder: Developmental aspects and effects of social context [Texte imprimé et/ou numérique] / A. Özge SUNGUR, Auteur ; Rainer K. W. SCHWARTING, Auteur ; Markus WÖHR, Auteur . - p.696-709. Langues : Anglais (eng) in Autism Research > 9-6 (June 2016) . - p.696-709 Mots-clés : animal model  postsynaptic density  neurodevelopmental disorders  autism  communication  ultrasonic vocalization  social context Index. décimale : PER Périodiques Résumé : Alterations in SHANK genes were repeatedly reported in autism spectrum disorder (ASD). ASD is a group of neurodevelopmental disorders diagnosed by persistent deficits in social communication/interaction across multiple contexts, with restricted/repetitive patterns of behavior. To date, diagnostic criteria for ASD are purely behaviorally defined and reliable biomarkers have still not been identified. The validity of mouse models for ASD therefore strongly relies on their behavioral phenotype. Here, we studied communication by means of isolation-induced pup ultrasonic vocalizations (USV) in the Shank1 mouse model for ASD by comparing Shank1?/? null mutant, Shank1+/? heterozygous, and Shank1+/+ wildtype littermate controls. The first aim of the present study was to evaluate the effects of Shank1 deletions on developmental aspects of communication in order to see whether ASD-related communication deficits are due to general impairment or delay in development. Second, we focused on social context effects on USV production. We show that Shank1?/? pups vocalized less and displayed a delay in the typical inverted U-shaped developmental USV emission pattern with USV rates peaking on postnatal day (PND) 9, resulting in a prominent genotype difference on PND6. Moreover, testing under social conditions revealed even more prominently genotype-dependent deficits regardless of the familiarity of the social context. As communication by definition serves a social function, introducing a social component to the typically nonsocial test environment could therefore help to reveal communication deficits in mouse models for ASD. Together, these results indicate that SHANK1 is involved in acoustic communication across species, with genetic alterations in SHANK1 resulting in social communication/interaction deficits. Autism Res 2016, 9: 696–709. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.1564 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=290

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

Naturally occurring low sociality in female rhesus monkeys: A tractable model for autism or not? / Ozge OZTAN in Molecular Autism, 15 (2024)  

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Use of the Zebrafish Model to Understand Behavioral Disorders Associated with Altered Oxytocin System Development: Implications for Autism and Prader–Willi Syndrome / Nicole JOHNSTON

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Developmental vitamin D deficiency increases foetal exposure to testosterone / Asad Amanat ALI in Molecular Autism, 11 (2020)  

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Loss of Cntnap2 in the Rat Causes Autism-Related Alterations in Social Interactions, Stereotypic Behavior, and Sensory Processing / Kaela E. SCOTT in Autism Research, 13-10 (October 2020)  

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CRISPR/Cas9-induced shank3b mutant zebrafish display autism-like behaviors / C. X. LIU in Molecular Autism, 9 (2018)  

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