Modeling Autistic Features in Animals

Division of Biology, California Institute of Technology, Pasadena, California 91125, USA.
Pediatric Research (Impact Factor: 2.31). 02/2011; 69(5 Pt 2):34R-40R. DOI: 10.1203/PDR.0b013e318212b80f
Source: PubMed


A variety of features of autism can be simulated in rodents, including the core behavioral hallmarks of stereotyped and repetitive behaviors, and deficits in social interaction and communication. Other behaviors frequently found in autism spectrum disorders (ASDs) such as neophobia, enhanced anxiety, abnormal pain sensitivity and eye blink conditioning, disturbed sleep patterns, seizures, and deficits in sensorimotor gating are also present in some of the animal models. Neuropathology and some characteristic neurochemical changes that are frequently seen in autism, and alterations in the immune status in the brain and periphery are also found in some of the models. Several known environmental risk factors for autism have been successfully established in rodents, including maternal infection and maternal valproate administration. Also under investigation are a number of mouse models based on genetic variants associated with autism or on syndromic disorders with autistic features. This review briefly summarizes recent developments in this field, highlighting models with face and/or construct validity, and noting the potential for investigation of pathogenesis, and early progress toward clinical testing of potential therapeutics. Wherever possible, reference is made to reviews rather than to primary articles.

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    • "In line with epidemiological studies, preclinical work has shown that maternal infection in laboratory animals induces autistic-like symptoms in the offspring. Rodent models of ASD induced by maternal infection are based on maternal respiratory infection with influenza virus or maternal immune activation (MIA) induced by polyinosine:cytosine , poly(I:C), a synthetic double-stranded RNA evoking an antiviral-like immune reaction, or by lipopolysaccharide (LPS), which evokes an antibacteriallike immune reaction (Patterson, 2011 "
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    ABSTRACT: Autism spectrum disorders (ASD) are among the most severe developmental psychiatric disorders known today, characterized by impairments in communication and social interaction and stereotyped behaviors. However, no specific treatments for ASD are as yet available. By enabling selective genetic, neural, and pharmacological manipulations, animal studies are essential in ASD research. They make it possible to dissect the role of genetic and environmental factors in the pathogenesis of the disease, circumventing the many confounding variables present in human studies. Furthermore, they make it possible to unravel the relationships between altered brain function in ASD and behavior, and are essential to test new pharmacological options and their side-effects. Here, we first discuss the concepts of construct, face, and predictive validity in rodent models of ASD. Then, we discuss how ASD-relevant behavioral phenotypes can be mimicked in rodents. Finally, we provide examples of environmental and genetic rodent models widely used and validated in ASD research. We conclude that, although no animal model can capture, at once, all the molecular, cellular, and behavioral features of ASD, a useful approach is to focus on specific autism-relevant behavioral features to study their neural underpinnings. This approach has greatly contributed to our understanding of this disease, and is useful in identifying new therapeutic targets.
    Behavioural pharmacology 09/2015; 26(6):522-540. DOI:10.1097/FBP.0000000000000163 · 2.15 Impact Factor
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    • "Maternal infection is well defined by epidemiological studies as a risk factor for neurodevelopmental disorders such as autism and schizophrenia (Hagberg et al., 2012; Depino, 2013; Meldrum et al., 2013). Mouse offspring that have been exposed to maternal infection display abnormalities reminiscent of the behavioral, histological, and molecular characteristics of autism (Patterson, 2011), while fetal brain infection does not cause these abnormalities (Meldrum et al., 2013). Mouse offspring exposed to maternal immune activation (MIA), which is elicited by poly-riboinosinic-polyribocytidylic acid or lipopolysaccharide, "
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    ABSTRACT: Prenatal exposure of the developing brain to various types of environmental stress increases susceptibility to neuropsychiatric disorders such as autism, attention deficit hyperactivity disorder and schizophrenia. Given that even subtle perturbations by prenatal environmental stress in the cerebral cortex impair the cognitive and memory functions, this review focuses on underlying molecular mechanisms of pathological cortical development. We especially highlight recent works that utilized animal exposure models, human specimens or/and induced Pluripotent Stem (iPS) cells to demonstrate: 1. molecular mechanisms shared by various types of environmental stressors, 2. the mechanisms by which the affected extracortical tissues indirectly impact the cortical development and function, and 3. interaction between prenatal environmental stress and the genetic predisposition of neuropsychiatric disorders. Finally, we discuss current challenges for achieving a comprehensive understanding of the role of environmentally disturbed molecular expressions in cortical maldevelopment, knowledge of which may eventually facilitate discovery of interventions for prenatal environment-linked neuropsychiatric disorders.
    Frontiers in Cellular Neuroscience 05/2015; 9. DOI:10.3389/fncel.2015.00207 · 4.29 Impact Factor
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    • "Language defi cits may be addressed in animal models by studying social communication mechanisms including ultrasonic vocalizations and scent marking (Crawley 2004, 2007, Patterson 2011, Roullet and Crawley 2011). One test for assessing social communications involves the evaluation of ultrasonic vocalizations in pups when outside the nest and maternal responses to these vocalizations; these tests are generally conducted between PND5 and PND12 (Crawley 2004, 2007, Roullet and Crawley 2011). "
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    ABSTRACT: Although animal models cannot exactly replicate human psychiatric disorders, they may be useful to investigate whether the behaviors associated with certain exposures in animals parallel those observed in people. According to the most current version of the Diagnostic and Statistical Manual of Mental Disorders, autism is diagnosed based on (1) persistent deficits in social communication and social interaction; and (2) the presence of restricted, repetitive patterns of behavior, interests and activities. To address whether developmental chlorpyrifos (CPF) exposure was associated with the development of autistic behaviors, a literature search was conducted to identify studies in rats and mice involving gestational or early postnatal exposure to CPF or CPF oxon (CPO, the active metabolite of CPF) and subsequent behavioral testing to assess behaviors related to autism. A total of 13 studies conducted in six different laboratories were identified. Analysis of these studies found that perinatal CPF exposure was generally associated with (1) no effect or increased social communications; (2) no effect or increased social encounters; (3) no effect, reduced stereotypies, or conflicting findings on stereotypic behaviors; and (4) no effect or increased preference for novelty and reduced anxiety in novel environments. These behavioral findings are generally inconsistent with the types of behaviors that would be expected in children with clinical autism. Based on the results of this analysis of rodent model studies involving CPF/CPO exposure, it cannot be concluded that gestational and/or perinatal CPF exposure is likely to be associated with the development of autism-like behaviors in humans.
    Critical Reviews in Toxicology 05/2014; 44(6):1-12. DOI:10.3109/10408444.2014.907772 · 5.10 Impact Factor
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