Inconsistent findings between laboratories are hampering scientific progress and are of increasing public concern. Differences in laboratory environment is a known factor contributing to poor reproducibility of findings between research sites, and well-controlled multisite efforts are an important next step to identify the relevant factors needed to reduce variation in study outcome between laboratories. Through harmonization of apparatus, test protocol, and aligned and non-aligned environmental variables, the present study shows that behavioral pharmacological responses in Shank2 knockout (KO) rats, a model of synaptic dysfunction relevant to autism spectrum disorders, were highly replicable across three research centers. All three sites reliably observed a hyperactive and repetitive behavioral phenotype in KO rats compared to their wild-type littermates as well as a dose-dependent phenotype attenuation following acute injections of a selective mGluR1 antagonist. These results show that reproducibility in preclinical studies can be obtained and emphasizes the need for high quality and rigorous methodologies in scientific research. Considering the observed external validity, the present study also suggests mGluR1 as potential target for the treatment of autism spectrum disorders.
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http://dx.doi.org/10.1038/s41598-019-47981-0 | DOI Listing |
J Neurodev Disord
January 2025
Graduate Neuroscience Program, University of California, Riverside, CA, USA.
Background: Fragile X syndrome (FXS) is a leading known genetic cause of intellectual disability and autism spectrum disorders (ASD)-associated behaviors. A consistent and debilitating phenotype of FXS is auditory hypersensitivity that may lead to delayed language and high anxiety. Consistent with findings in FXS human studies, the mouse model of FXS, the Fmr1 knock out (KO) mouse, shows auditory hypersensitivity and temporal processing deficits.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Bio and Brain Engineering, KAIST, Daejeon, 34141, Republic of Korea.
Autism spectrum disorder (ASD) affects up to 1 in 59 children, and is one of the most common neurodevelopmental disorders. Recent genomic studies have highlighted the role of rare variants in ASD. This study aimed to identify genes affected by rare variants shared by siblings with ASD and validate the function of a candidate gene FRRS1L.
View Article and Find Full Text PDFJ Intellect Disabil
January 2025
Pro Vice Chancellor, Staffordshire University, UK.
Background: Autism spectrum disorder poses challenges in social communication and behavior, while Intellectual disabilities are characterized by deficits in cognitive, social, and adaptive skills, frequently accompanied by stereotypies and challenging behaviors. Despite the progress made in autism spectrum disorder research, there is often a lack of research focusing on individuals with co-occurring autism spectrum disorder and intellectual disability. Robot-assisted autism therapies are effective in addressing these needs.
View Article and Find Full Text PDFJ Commun Disord
November 2024
Department of English Literature and Linguistics, Bar-Ilan University, Israel; Gonda Multidisciplinary Brain Research Center, Bar-Ilan University, Israel. Electronic address:
Introduction: Autism spectrum disorder (ASD) is characterized by impairments in social interactions, social communication, and repetitive and stereotyped patterns of behavior. Previous studies have reported mixed findings regarding the links between language (i.e.
View Article and Find Full Text PDFJ Neurosci
January 2025
Arizona State University, Department of Psychology, Tempe, AZ, 85287 USA.
The cerebellum, identified to be active during cognitive and social behavior, has multisynaptic connections through the cerebellar nuclei (CN) and thalamus to cortical regions, yet formation and modulation of these pathways are not fully understood. Perineuronal nets (PNNs) respond to changes in local cellular activity and emerge during development. PNNs are implicated in learning and neurodevelopmental disorders, but their role in the CN during development is unknown.
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