title: The effects of aging on the BTBR mouse model of autism spectrum disorder.
abstract: Autism spectrum disorder (ASD) is a complex heterogeneous neurodevelopmental disorder characterized by alterations in social functioning, communicative abilities, and engagement in repetitive or restrictive behaviors. The process of aging in individuals with autism and related neurodevelopmental disorders is not well understood, despite the fact that the number of individuals with ASD aged 65 and older is projected to increase by over half a million individuals in the next 20 years. To elucidate the effects of aging in the context of a modified central nervous system, we investigated the effects of age on the BTBR T + tf/j mouse, a well characterized and widely used mouse model that displays an ASD-like phenotype. We found that a reduction in social behavior persists into old age in male BTBR T + tf/j mice. We employed quantitative proteomics to discover potential alterations in signaling systems that could regulate aging in the BTBR mice. Unbiased proteomic analysis of hippocampal and cortical tissue of BTBR mice compared to age-matched wild-type controls revealed a significant decrease in brain derived 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 these proteins, including "Neural synaptic plasticity regulation" and "Neurotransmitter secretion regulation." Taken together, these results contribute to our understanding of the effects of aging on an ASD-like mouse model in regards to both behavior and protein alterations, though additional studies are needed to fully understand the complex interplay underlying aging in mouse models displaying an ASD-like phenotype.
authors.affiliation: Metabolism Unit, Laboratory of Clinical Investigation, National Institutes of Health, National Institute on Aging Baltimore, MD, USA ; Department of Neurology, Johns Hopkins University School of Medicine, Kennedy Krieger Institute Baltimore, MD, USA.
authors.forename: Joan M
authors.initials: JM
authors.lastname: Jasien
authors.affiliation: Metabolism Unit, Laboratory of Clinical Investigation, National Institutes of Health, National Institute on Aging Baltimore, MD, USA.
authors.forename: Caitlin M
authors.initials: CM
authors.lastname: Daimon
authors.affiliation: Metabolism Unit, Laboratory of Clinical Investigation, National Institutes of Health, National Institute on Aging Baltimore, MD, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Kennedy Krieger Institute Baltimore, MD, USA.
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Shapiro
authors.affiliation: Metabolism Unit, Laboratory of Clinical Investigation, National Institutes of Health, National Institute on Aging Baltimore, MD, USA.
authors.forename: Bronwen
authors.initials: B
authors.lastname: Martin
authors.affiliation: Receptor Pharmacology Unit, Laboratory of Neurosciences, National Institute on Aging Baltimore, MD, USA ; VIB-Department of Molecular Genetics, University of Antwerp Antwerp, Belgium.
authors.forename: Stuart
authors.initials: S
authors.lastname: Maudsley
keywords: ASD; BDNF; BTBR; aging; autism; neurodevelopmental disorder; neuroprotection; synaptic marker