Modeling Restricted Repetitive Behavior in Animals / Allison BECHARD in Autism - Open Access, 2-S ([01/12/2012])  

Public ISBD [article]  inAutism - Open Access > 2-S [01/12/2012] . - 8 p. Titre : Modeling Restricted Repetitive Behavior in Animals Type de document : texte imprimé Auteurs : Allison BECHARD, Auteur ; Mark LEWIS, Auteur Article en page(s) : 8 p. Langues : Anglais (eng) Mots-clés : Repetitive behavior  Stereotypy  Cortical-basal ganglia circuitry  Autism spectrum disorders Index. décimale : PER Périodiques Résumé : Restricted, repetitive behavior is one of the three diagnostic domains for autism spectrum disorders, and commonly observed in a number of other neurodevelopmental disorders. Despite its clinical significance, effective treatments for restricted, repetitive behavior are limited including few, if any, pharmacological interventions with demonstrated efficacy. This is in large measure due to the lack of knowledge of the pathophysiological mechanisms that mediate the development and expression of repetitive behaviors in autism spectrum disorders. Therefore, animal models, particularly those that encompass both lower order and higher order repetitive behaviors, could be particularly useful. Such models could identify various potential etiologies, characterize commonalities in pathophysiology, identify novel potential therapeutic targets, and guide the development and validation of novel treatments. We have organized existing models of restricted, repetitive behavior in animals into four different categories: repetitive behavior resulting from a specific CNS insult (e.g. genetic mutation); repetitive behavior induced by specific pharmacological agents (e.g. amphetamine); repetitive behavior consequent to confined or restricted housing (e.g. laboratory caging); and repetitive behavior associated with specific inbred mouse strains. We have reviewed the literature from each of these categories of animal models, and discuss their multiple etiologies in light of a potential shared common pathophysiology: alterations in cortical-basal ganglia circuitry. Our own work with deer mice as a model of restricted, repetitive behavior suggests reduced activity in the indirect pathway of the basal ganglia, and has identified novel potential therapeutic targets. Other promising models are emerging that can take full advantage of modern genetics and molecular neuroscience that can be used to elucidate the pathophysiology of restricted, repetitive behavior. However, much more work must be done in this area to uncover the mechanisms underlying restricted, repetitive behavior, a critical step in finding effective new treatments for individuals with autism spectrum disorders. En ligne : https://dx.doi.org/10.4172/2165-7890.S1-006 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Modeling Restricted Repetitive Behavior in Animals [texte imprimé] / Allison BECHARD, Auteur ; Mark LEWIS, Auteur . - 8 p. Langues : Anglais (eng) in Autism - Open Access > 2-S [01/12/2012] . - 8 p. Mots-clés : Repetitive behavior  Stereotypy  Cortical-basal ganglia circuitry  Autism spectrum disorders Index. décimale : PER Périodiques Résumé : Restricted, repetitive behavior is one of the three diagnostic domains for autism spectrum disorders, and commonly observed in a number of other neurodevelopmental disorders. Despite its clinical significance, effective treatments for restricted, repetitive behavior are limited including few, if any, pharmacological interventions with demonstrated efficacy. This is in large measure due to the lack of knowledge of the pathophysiological mechanisms that mediate the development and expression of repetitive behaviors in autism spectrum disorders. Therefore, animal models, particularly those that encompass both lower order and higher order repetitive behaviors, could be particularly useful. Such models could identify various potential etiologies, characterize commonalities in pathophysiology, identify novel potential therapeutic targets, and guide the development and validation of novel treatments. We have organized existing models of restricted, repetitive behavior in animals into four different categories: repetitive behavior resulting from a specific CNS insult (e.g. genetic mutation); repetitive behavior induced by specific pharmacological agents (e.g. amphetamine); repetitive behavior consequent to confined or restricted housing (e.g. laboratory caging); and repetitive behavior associated with specific inbred mouse strains. We have reviewed the literature from each of these categories of animal models, and discuss their multiple etiologies in light of a potential shared common pathophysiology: alterations in cortical-basal ganglia circuitry. Our own work with deer mice as a model of restricted, repetitive behavior suggests reduced activity in the indirect pathway of the basal ganglia, and has identified novel potential therapeutic targets. Other promising models are emerging that can take full advantage of modern genetics and molecular neuroscience that can be used to elucidate the pathophysiology of restricted, repetitive behavior. However, much more work must be done in this area to uncover the mechanisms underlying restricted, repetitive behavior, a critical step in finding effective new treatments for individuals with autism spectrum disorders. En ligne : https://dx.doi.org/10.4172/2165-7890.S1-006 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

The pathophysiology of restricted repetitive behavior / Mark LEWIS in Journal of Neurodevelopmental Disorders, 1-2 (June 2009)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 1-2 (June 2009) . - p.114-32 Titre : The pathophysiology of restricted repetitive behavior Type de document : texte imprimé Auteurs : Mark LEWIS, Auteur ; Soo-Jeong KIM, Auteur Article en page(s) : p.114-32 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Restricted, repetitive behaviors (RRBs) are heterogeneous ranging from stereotypic body movements to rituals to restricted interests. RRBs are most strongly associated with autism but occur in a number of other clinical disorders as well as in typical development. There does not seem to be a category of RRB that is unique or specific to autism and RRB does not seem to be robustly correlated with specific cognitive, sensory or motor abnormalities in autism. Despite its clinical significance, little is known about the pathophysiology of RRB. Both clinical and animal models studies link repetitive behaviors to genetic mutations and a number of specific genetic syndromes have RRBs as part of the clinical phenotype. Genetic risk factors may interact with experiential factors resulting in the extremes in repetitive behavior phenotypic expression that characterize autism. Few studies of individuals with autism have correlated MRI findings and RRBs and no attempt has been made to associate RRB and post-mortem tissue findings. Available clinical and animal models data indicate functional and structural alterations in cortical-basal ganglia circuitry in the expression of RRB, however. Our own studies point to reduced activity of the indirect basal ganglia pathway being associated with high levels of repetitive behavior in an animal model. These findings, if generalizable, suggest specific therapeutic targets. These, and perhaps other, perturbations to cortical basal ganglia circuitry are mediated by specific molecular mechanisms (e.g., altered gene expression) that result in long-term, experience-dependent neuroadaptations that initiate and maintain repetitive behavior. A great deal more research is needed to uncover such mechanisms. Work in areas such as substance abuse, OCD, Tourette syndrome, Parkinson's disease, and dementias promise to provide findings critical for identifying neurobiological mechanisms relevant to RRB in autism. Moreover, basic research in areas such as birdsong, habit formation, and procedural learning may provide additional, much needed clues. Understanding the pathophysioloy of repetitive behavior will be critical to identifying novel therapeutic targets and strategies for individuals with autism. En ligne : http://dx.doi.org/10.1007/s11689-009-9019-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=341 [article] The pathophysiology of restricted repetitive behavior [texte imprimé] / Mark LEWIS, Auteur ; Soo-Jeong KIM, Auteur . - p.114-32. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 1-2 (June 2009) . - p.114-32 Index. décimale : PER Périodiques Résumé : Restricted, repetitive behaviors (RRBs) are heterogeneous ranging from stereotypic body movements to rituals to restricted interests. RRBs are most strongly associated with autism but occur in a number of other clinical disorders as well as in typical development. There does not seem to be a category of RRB that is unique or specific to autism and RRB does not seem to be robustly correlated with specific cognitive, sensory or motor abnormalities in autism. Despite its clinical significance, little is known about the pathophysiology of RRB. Both clinical and animal models studies link repetitive behaviors to genetic mutations and a number of specific genetic syndromes have RRBs as part of the clinical phenotype. Genetic risk factors may interact with experiential factors resulting in the extremes in repetitive behavior phenotypic expression that characterize autism. Few studies of individuals with autism have correlated MRI findings and RRBs and no attempt has been made to associate RRB and post-mortem tissue findings. Available clinical and animal models data indicate functional and structural alterations in cortical-basal ganglia circuitry in the expression of RRB, however. Our own studies point to reduced activity of the indirect basal ganglia pathway being associated with high levels of repetitive behavior in an animal model. These findings, if generalizable, suggest specific therapeutic targets. These, and perhaps other, perturbations to cortical basal ganglia circuitry are mediated by specific molecular mechanisms (e.g., altered gene expression) that result in long-term, experience-dependent neuroadaptations that initiate and maintain repetitive behavior. A great deal more research is needed to uncover such mechanisms. Work in areas such as substance abuse, OCD, Tourette syndrome, Parkinson's disease, and dementias promise to provide findings critical for identifying neurobiological mechanisms relevant to RRB in autism. Moreover, basic research in areas such as birdsong, habit formation, and procedural learning may provide additional, much needed clues. Understanding the pathophysioloy of repetitive behavior will be critical to identifying novel therapeutic targets and strategies for individuals with autism. En ligne : http://dx.doi.org/10.1007/s11689-009-9019-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=341

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