Inflammatory profiles in the BTBR mouse: How relevant are they to autism spectrum disorders?

Careaga, Milo; Schwartzer, Jared J.; Ashwood, Paul

doi:10.1016/j.bbi.2014.06.006

Cited by 66 publications

(45 citation statements)

References 61 publications

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“…BTBR mice have revealed a number of immune abnormalities several of which observed in children with ASD [21]. The neuroimmune relation in the BTBR mice is characterized by higher pro-inflammatory signaling and diminished social interactions [52,53]. BTBR mice showed the elevated expression levels of cytokines in the brain [24].…”

Section: Discussionmentioning

confidence: 98%

Immune Alterations in CD8+ T Cells Are Associated with Neuronal C-C and C-X-C Chemokine Receptor Regulation Through Adenosine A2A Receptor Signaling in a BTBR T+ Itpr3tf/J Autistic Mouse Model

et al. 2017

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Associative studies on a range of neurodevelopmental disorders have identified relationships between behavioral deficits and immune system function. The BTBR T Itpr3/J (BTBR) mouse strain displays aberrant characteristics in its social behavior and immune responses, providing a significant opportunity to examine the relationship between behavior and the immune system. This study investigated the influence of adenosine A2A receptor activity on C-C and C-X-C chemokine receptors involved in autism in the BTBR mouse model. A2A receptors have previously been targeted in clinical trials by potential therapeutics with neuroprotective, immunomodulatory, and analgesic properties. In this study, we examined the effects of A2A receptor antagonist SCH5826 (SCH) and A2A receptor agonist CGS21680 (CGS) on C-C and C-X-C chemokine receptors (CCR3, CCR4, CCR5, CCR6, CCR7, CXCR3, CXCR4, and CXCR5) on splenic CD8 T cells in the BTBR autistic mouse model. We also assessed the C-C and C-X-C chemokine receptors mRNA levels in brain tissue. Our results showed that CCR3, CCR4, CCR5, CCR6, CCR7, CXCR3, CXCR4, and CXCR5 production in splenic CD8 T cells decreased significantly in BTBR-CGS-treated mice in comparison with that in BTBR control and BTBR-SCH-treated mice. In addition, RT-PCR analysis revealed decreased gene expression levels for C-C and C-X-C chemokine receptors in the brain tissue of BTBR-CGS-treated mice, whereas these levels were significantly increased in BTBR control and BTBR-SCH-treated mice. Our results suggest that treating BTBR mice with CGS decreases C-C and C-X-C chemokine receptor signaling and might therefore provide a unique avenue for developing future therapies for autism and neuroimmunological disorders.

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Section: Discussionmentioning

confidence: 98%

Immune Alterations in CD8+ T Cells Are Associated with Neuronal C-C and C-X-C Chemokine Receptor Regulation Through Adenosine A2A Receptor Signaling in a BTBR T+ Itpr3tf/J Autistic Mouse Model

et al. 2017

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“…The BTBR T + Itpr3 tf /J (BTBR) inbred mouse strain is a well characterized animal model exhibiting several behaviors relevant to the core features of ASD, including reduced social interactions, repetitive behavior, and atypical vocalizations (for review see (Careaga et al, 2015b)). Compared to the highly social C57BL/6J (C57) strain, BTBR mice exhibit heightened inflammatory phenotypes in the peripheral immune system and central nervous system, characteristics often reported in individuals with ASD (Careaga et al, 2015b).…”

Section: Introductionmentioning

confidence: 99%

“…Compared to the highly social C57BL/6J (C57) strain, BTBR mice exhibit heightened inflammatory phenotypes in the peripheral immune system and central nervous system, characteristics often reported in individuals with ASD (Careaga et al, 2015b). For example, BTBR mice show signs of increased microglia activation (Heo et al, 2011), a marker of neuroinflammation also reported in individuals with ASD (Morgan et al, 2010; Suzuki et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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

Schwartzer

Onore

Rose

et al. 2017

Brain, Behavior, and Immunity

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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.

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“…A recent study also demonstrated that children with ASD are more likely to have middle ear infections and otitis-related complications than healthy counterparts [3] . A dysregulated or abnormal immune response in children with ASD has been considered to play a potential and yet undetermined role in the etiology of autism [4,5] . Immune system abnormalities in children with autism include both enhanced autoimmunity and reduced immune function [6] .…”

Section: Resultsmentioning

confidence: 99%

Salivary IgA Correlate with Recurrent Respiratory Infections and Hyperreactivity in Children with Autism

Furland

Sindelar²

2016

International Journal of Neurology Research

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AIM: Autism spectrum disorders (ASD) are characterized by impairment in social interactions, communication deficits, and restricted interests and behaviors. Accumulating evidence suggests that dysregulation of the immune system may be involved in the pathophysiology of ASD. The aim of the study was to assess if the severity of clinical and behavioral parameters of autistic children was associated with low levels of secretory IgA (sIgA) in saliva. We hypothesized that a decreased immune response in children with autism would decrease the levels of sIgA, as is the predominant antibody isotype in saliva and a marker of mucosal immunity. MATERIALS AND METHODS: Saliva samples were obtained from 3-10 year-old children with ASD and age-matched typically developing Caucasian children from Patagonia region, Argentina. RESULTS AND CONCLUSIONS: Autistic children with reduced levels of salivary IgA had a higher incidence of upper respiratory diseases compared to the controls. The reduction in sIgA levels also correlated inversely with the severity of the behavioral disorders. The patients with the most severe impairment in autism-related behaviors had the lowest levels of sIgA in the cohort studied. These findings suggest that sIgA could be an early indicator and possibly a biomarker of the dysregulation of the immune system in some children with autism. The characterization of immunological parameters in ASD has important implications for detection of a subset of individuals with ASD, and should be considered when designing therapeutic strategies to treat core symptoms and behavioral impairments of ASD.

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Inflammatory profiles in the BTBR mouse: How relevant are they to autism spectrum disorders?

Cited by 66 publications

References 61 publications

Immune Alterations in CD8+ T Cells Are Associated with Neuronal C-C and C-X-C Chemokine Receptor Regulation Through Adenosine A2A Receptor Signaling in a BTBR T+ Itpr3tf/J Autistic Mouse Model

Immune Alterations in CD8+ T Cells Are Associated with Neuronal C-C and C-X-C Chemokine Receptor Regulation Through Adenosine A2A Receptor Signaling in a BTBR T+ Itpr3tf/J Autistic Mouse Model

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

Salivary IgA Correlate with Recurrent Respiratory Infections and Hyperreactivity in Children with Autism

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