An overview of modeling and behavioral assessment of autism in the rodent

Abstract

Autism Spectrum Disorders (ASDs) are common neurodevelopmental disorders with a growing incidence that generally present in the first 3 years of life. Behavioral symptoms, including impaired social interaction and increased repetitive or stereotypic movements, are hallmark characteristics of autism. Animal models are research tools used to study the biology of the disease and to develop new therapeutic approaches. The complexity of the etiology of autism makes it challenging to develop a comprehensive animal model that accurately mimics different clinical aspects of autism. Here, we reviewed the literature on modeling and behavioral assessment of autism in the rodent, and focused on ASD behavioral phenotypes that can be modeled in rodents. These animal models can be effective in gaining a better understanding of the pathophysiology of the disease.

ASD-like behaviors, a dysregulated inflammatory response and decreased expression of PLP1 characterize mice deficient for sialyltransferase ST3GAL5

“…These abnormalities are reminiscent of the established phenotypes of ASD in clinic ( Thapar et al., 2017 ) and in animal models ( Haratizadeh et al., 2021 ). The Diagnostic and Treatment Manual for Mental Disorders, Fifth Edition (DSM-5) defines ASD by the expression of deficient social communication and interaction, restricted-repetitive behaviours and developmental impairments (DSM-5R, 2013).…”

“…The Diagnostic and Treatment Manual for Mental Disorders, Fifth Edition (DSM-5) defines ASD by the expression of deficient social communication and interaction, restricted-repetitive behaviours and developmental impairments (DSM-5R, 2013). The core ASD-like characteristics in rodents can be recapitulated by the expression of aberrant reciprocal social behavior, stereotypy and cognitive deficits ( Haratizadeh et al., 2021 , Veniaminova et al., 2017 , Veniaminova et al., 2020 ).…”

“…Social behaviours were also abnormally altered by the administration of LPS which is in keeping with findings that LPS exacerbates ASD-like behaviours in other mouse models including BTBR mice, a genetic model of ASD ( Das et al., 2019 ; McFarlane et al., 2008 ; Onore et al., 2013 ). The impaired conditioned taste conditioning suggests cognitive rigidity in St3gal5−/− animals, an important element of ASD-like phenotype ( Haratizadeh et al., 2021 ). The presence of motor deficits in the St3gal5−/− mice also agrees with other studies in which an association between ASD syndrome and motor dyscoordination has been described ( Das et al., 2019 ; Lewis et al., 2007 ; Thapar et al., 2017 ).…”

“…Here, we hypothesized that St3gal5−/− mice would display features of neuropsychiatric developmental pathologies and that these changes, given the anti-inflammatory actions of brain gangliosides, would be exacerbated by an inflammatory challenge with LPS. Therefore, we studied male and female St3gal5−/− mice for social, restricted-repetitive behaviours to determine whether the animals would display ASD-like features ( Haratizadeh et al., 2021 ), as well as evaluation of inhibitory learning and the expression of myelination and inflammation markers in brain cortex and spleen.…”

Complex social behaviour during an extended period of time in a valproic acid animal model of autism spectrum disorder

“…Social deficits are one the two hallmarks of ASD symptoms as defined by the American Manual of Psychiatry in its latest version 1 . As face validity is key in animal modeling of diseases and disorders, it has become mandatory for ASD animal models, whether genetic or environmental, to express some forms of social deficits before being considered for further analysis and characterization 19,20,23–25 .…”