-
Brain, Behavior, and Immunity May 2020In recent years, clinical studies have shown strong epidemiological evidence of an increased risk of developing neuropsychiatric disorders after childhood exposure to...
In recent years, clinical studies have shown strong epidemiological evidence of an increased risk of developing neuropsychiatric disorders after childhood exposure to streptococcal infection, including the Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection (PANDAS). New preclinical studies on group A streptococcus (GAS) exposure investigate how to disentangle the influences of immune activation to induce long-term neurobehavioral effects associated with neuropsychiatric disorders such as obsessive-compulsive disorder, schizophrenia or autism. The present systematic review collects neurobehavioral evidence regarding the use of GAS exposure in animal models to study the vulnerability to different neuropsychiatric disorders, improving our understanding of its possible causes and consequences, and compares its contribution with other preclinical models of immune activation in a variety of paradigms. Specifically, we reviewed the effects of postnatal GAS exposure, in comparison with post- and prenatal exposure to Lipopolysaccharide (LPS) and Polyinosinic:polycytidylic acid (Poly I:C), on the long-term effects concerning psychomotor, cognition and socioemotional outcomes in rodents. GAS exposure in animal models has revealed different behavioral alterations such as reduced locomotion and motor coordination, a deficit in sensorimotor gating, learning, working memory, altered social behavior, and increased anxiety and stereotyped behavior. Most of the results found are in accordance with other immune activation models -LPS and Poly I:C-, with some discrepancies. The systematic review of the literature supports the preclinical model of GAS exposure as a valid model for studying the neurobehavioral consequences of streptococcal infections. Future studies on streptococcal infection could contribute increasing our knowledge on preventive actions or treatments for neuropsychiatric disorders.
Topics: Animals; Autistic Disorder; Autoimmune Diseases; Child; Humans; Obsessive-Compulsive Disorder; Schizophrenia; Streptococcal Infections; Streptococcus pyogenes
PubMed: 30818033
DOI: 10.1016/j.bbi.2019.02.027 -
Molecular Autism 2019Autism (MIM 209850) is a multifactorial disorder with a broad clinical presentation. A number of high-confidence ASD risk genes are known; however, the contribution of...
Autism (MIM 209850) is a multifactorial disorder with a broad clinical presentation. A number of high-confidence ASD risk genes are known; however, the contribution of non-genetic environmental factors towards ASD remains largely uncertain. Here, we present a bioinformatics resource of genetic and induced models of ASD developed using a shared annotation platform. Using this data, we depict the intricate trends in the research approaches to analyze rodent models of ASD. We identify the top 30 most frequently studied phenotypes extracted from rodent models of ASD based on 787 publications. As expected, many of these include animal model equivalents of the "core" phenotypes associated with ASD, such as impairments in social behavior and repetitive behavior, as well as several comorbid features of ASD including anxiety, seizures, and motor-control deficits. These phenotypes have also been studied in models based on a broad range of environmental inducers present in the database, of which gestational exposure to valproic acid (VPA) and maternal immune activation models comprising lipopolysaccharide (LPS) and poly I:C are the most studied. In our unique dataset of rescue models, we identify 24 pharmaceutical agents tested on established models derived from various ASD genes and CNV loci for their efficacy in mitigating symptoms relevant for ASD. As a case study, we analyze a large collection of Shank3 mouse models providing a high-resolution view of the in vivo role of this high-confidence ASD gene, which is the gateway towards understanding and dissecting the heterogeneous phenotypes seen in single-gene models of ASD. The trends described in this study could be useful for researchers to compare ASD models and to establish a complete profile for all relevant animal models in ASD research.
Topics: Animals; Autistic Disorder; Databases, Genetic; Disease Models, Animal; Mice; Phenotype; Rats; Translational Research, Biomedical
PubMed: 30911366
DOI: 10.1186/s13229-019-0263-7