C57BL/6J bone marrow transplant increases sociability in BTBR T+ Itpr3tf/J mice

Abstract

Associative studies across a range of neurodevelopmental disorders have revealed a relationship between immune system function and behavioral deficits. These correlations are particularly evident in individuals with autism spectrum disorders (ASD), a developmental disorder characterized by social behavior deficits and noted for its high instances of immune system dysfunction. Mouse models provide a unique opportunity to explore causal links between immune and nervous system function and reveal how changes in these systems alter behavioral profiles. The BTBR T+ Itpr3tf/J (BTBR) mouse strain is characterized by both social behavior impairments and aberrant immune responses, affording the unique opportunity to investigate the causal relationship between behavior and immunity through direct manipulation of these systems. Using bone marrow from the highly social C57BL/6J (C57) mouse strain, BTBR mice were tested for changes in social approach behavior and repetitive grooming following irradiation and bone marrow transplant. BTBR recipient mice treated with allogeneic bone marrow from C57 donor mice, but not syngeneic BTBR bone marrow, displayed increased sociability as measured by the three-chamber social approach task and total time spent social sniffing. In addition, C57 recipient mice given allogeneic bone marrow from BTBR donors showed a significant increase in repetitive grooming behavior. These data provide evidence for a causal relationship between peripheral immune phenotype and social behavior in the BTBR mouse strain and further strengthen and expand on our existing understanding of the role of immune function in behavior.

Sex-Dependent Effects of Perinatal Inflammation on the Brain: Implication for Neuro-Psychiatric Disorders

“…The inbred mouse strain BTBR T+ tf/J (BTBR) exhibit deficits that mimic core behavioral changes in autism [193] and interestingly, sex-related alterations of gut microbiota composition were shown in the BTBR ASD mouse model [194]. This mouse model has also provided evidence for a causal relationship between peripheral immune phenotype and social behavior by demonstrating that bone marrow transplant from control mice increases sociability in BTBR ASD mice [195].…”

Specificity in Sociality: Mice and Prairie Voles Exhibit Different Patterns of Peer Affiliation

“…The three-chambered sociability/social preference test (also called the Crawley sociability test) was devised in 2004 as a modification of the PPT and other social tests, specifically oriented toward measuring social approach. It has been widely used to assess both sociability and social preferences in mice (Moy et al, 2004 , 2007 ; Nadler et al, 2004 ; Schwartzer et al, 2017 ), with similar tests used in rats (Smith et al, 2015 , 2017 ). To assess sociability, mice are typically given a choice between a novel object (an empty wire pencil cup) and a social stimulus (a pencil cup covering a novel mouse).…”

A Review of Oxytocin and Arginine-Vasopressin Receptors and Their Modulation of Autism Spectrum Disorder

“…To date, this technique has allowed researchers to manipulate genetic information (Halladay et al, 2009 ), allowing control over genetic factors that contribute to the development of neurodevelopmental disorders, potentially giving rise to new medical treatments (Avraham et al, 2017 ). Rodent models have been adopted in ASD studies to investigate mechanisms for prevention (Vuillermot et al, 2017 ), and potential therapeutic treatments (Chadman, 2017 ; Guoynes et al, 2017 ), as well as to better understand the involvement of the gut-brain axis (for a review see Nithianantharajah et al, 2017 ) and the immune system (Schwartzer et al, 2017 ) in ASD etiology. To illustrate this, we draw specific attention to the pivotal role that animal models have played in elucidating how maternal immune activation, a well-ascertained environmental risk factor, contributes to ASD.…”