Frontiers in Aging Neuroscience (Sep 2014)
The Effects of aging on the BTBR mouse model of autism spectrum disorder
Abstract
Autism spectrum disorders (ASD) are complex, heterogeneous neurodevelopmental disorderscharacterized by alterations in social functioning, communicative abilities, and engagement inrepetitive or restrictive behaviors. The process of aging in individuals with autism and relatedneurodevelopmental disorders is not well understood, despite the fact that the number ofindividuals with ASD aged 65 and older is projected to increase by over half a millionindividuals in the next 20 years. To elucidate the effects of aging in the context of a modifiedcentral nervous system, we investigated the effects of age on the BTBR T+tf/j mouse, a wellcharacterized and widely used mouse model that displays an ASD-like phenotype. We found thata reduction in social behavior persists into old age in male BTBR T+tf/j mice. We employedquantitative proteomics to discover potential alterations in signaling systems that could regulateaging in the BTBR mice. Unbiased proteomic analysis of hippocampal and cortical tissue ofBTBR mice compared to age-matched wild-type controls revealed a significant decrease in brainderived neurotrophic factor and significant increases in multiple synaptic markers (spinophilin,Synapsin I, PSD 95, NeuN), as well as distinct changes in functional pathways related to theseproteins, including Neural synaptic plasticity regulation and Neurotransmitter secretionregulation. Taken together, these results contribute to our understanding of the effects of agingon an ASD-like mouse model in regards to both behavior and protein alterations, thoughadditional studies are needed to fully understand the complex interplay underlying aging inmouse models displaying an ASD-like phenotype.
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