Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2011 May;69(5 Pt 2):34R-40R.
doi: 10.1203/PDR.0b013e318212b80f.

Modeling Autistic Features in Animals

Affiliations
Free PMC article
Review

Modeling Autistic Features in Animals

Paul H Patterson. Pediatr Res. .
Free PMC article

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 (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.

Figures

Figure 1
Figure 1. Summary of MIA-induced effects on the placenta
Maternal injection of poly(I:C) activates the maternal immune system, elevating pro-inflammatory factors, including IL-6, which enters the spiral arteries that descend through the decidua and spongiotrophoblast layers, filling the maternal bloodspaces of the labyrinth. Resident immune cells in the decidua are activated to express CD69 and further propagate the inflammatory response. IL-6 derived from decidual cells acts in a paracrine manner on target cells in the spongiotrophoblast layer. Ligation with the cognate receptor IL-6Ra with gp130 leads to JAK/STAT3 activation and increases in acute phase proteins, such as SOCS3, and downregulation of placental growth hormone (GH) production. This leads to reduced insulin-like growth factor binding protein 3 (IGFBP3) and IGFI. Global changes in STAT3 activation in the spongiotrophoblast layer alters the production of placenta-specific pro-lactin protein (PLP) and other pro-lactin proteins. These changes in endocrine factors are very likely to lead to acute placental pathophysiology and subsequent effects on fetal development. Reprinted from Hsiao EY, Patterson PH Brain Behav Immun doi:10.1016/j.bbi.2010.12.017; Copyright © 2010 Elsevier, Ltd. with permission.
Figure 2
Figure 2. A social network for autism susceptibility candidate genes
Analysis of the relationships between 33 autism candidate genes (red emblems) and associated syndrome genes (green emblems) was carried out using the Ingenuity pathway analysis. Direct (solid lines) and indirect (dashed lines) associations between the candidate genes demonstrate the close relationships between these genes. Recently published interactions linking FMR1, CYFIP1, and JAKMIP1 by gene regulation, and A2BP1 (FOX1) with NLGN3 by splicing regulation were added as custom interactions (blue lines). The androgen receptor (orange emblem) and three of its interactions with candidate genes (orange lines) are highlighted to demonstrate the correlation with the extreme male brain hypothesis. (Reprinted from Bill BR and Geschwind DH Curr Opin Genetics Devel 19:271–278; Copyright © 2010 Elsevier, Ltd. with permission)

Similar articles

See all similar articles

Cited by 46 articles

See all "Cited by" articles

Publication types

Feedback