Modeling Autistic Features in Animals

Abstract

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 (ASD) 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, as well as 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 towards clinical testing of potential therapeutics. Wherever possible, reference is made to reviews rather than primary articles.

Long-Term Memory Deficits are Associated with Elevated Synaptic ERK1/2 Activation and Reversed by mGluR5 Antagonism in an Animal Model of Autism

“…While many models of autism have been described (Moy et al, 2006;Patterson, 2011;Silverman et al, 2010b), the BTBR mice are unusual in that the autism-like phenotype arose spontaneously as opposed to being the result of genetic manipulation. Importantly, these mice exhibit behaviors that align with the three diagnostic criteria for autism (McFarlane et al, 2008;Scattoni et al, 2011).…”

“…A significant proportion of persons diagnosed with autism exhibit intellectual disability, yet no effective treatment exists for these cognitive impairments (Baio, 2012;Bryson et al, 2008;Fombonne, 2006;La Malfa et al, 2004). The complex phenotypes of autism are difficult to model in mice (Moy et al, 2006;Patterson, 2011;Silverman et al, 2010b), thereby slowing the development of successful therapies. Nonetheless, the three diagnostic criteria of autism (eg, impaired sociability, abnormal communication, and excessive stereotypic behaviors) are expressed by the BTBR T þ Itpr3 tf /J (formerly BTBR T þ tf/J and hereafter 'BTBR') inbred strain (McFarlane et al, 2008;Meyza et al, 2013;Scattoni et al, 2011).…”

Immune Privilege Revisited: The Roles of Neuronal MHC Class I Molecules in Brain Development and Plasticity

“…Current research efforts are focused on elucidating the consequences of prenatal immune insult on the brain development, so called "maternal immune activation". Both schizophrenia and autism have been genetically linked to MHC cluster and to prenatal immune insult (Soumiya et al 2011, Buehler 2011, Escobar et al 2011, Patterson 2011, Fatemi et al 2011, Parker-Athill and Tan 2010, Boksa 2010, Currenti 2010, Li et al 2009, Patterson 2009, Smith et al 2007, Cohly and Panja 2005, Patterson 2002, Stubbs and Magenis 1980. Future studies will no doubt elucidate the interactions between the nervous and immune systems in more detail, as well as shed more light on the vast polymorphism of MHC class I molecules, especially in the light of their neuronal functions.…”

An Evolutionary Biology Approach to Understanding Neurological Disorders

“…A greater understanding of the genetics underlying SCZ will also inform the development of future animal models. Likewise, for ASD, there are a wide variety of animal models available, which are becoming increasingly well characterized (Patterson, 2011;Tordjman et al, 2007). These include naturally-bred rodents (Gilby, 2008;Pearson et al, 2010) and transgenic mouse models (Minshew & McFadden, 2011;Robertson & Feng, 2011).…”