The Immune System in Autism

Heuer, Luke; Ashwood, Paul; Water, Judy Van de

doi:10.1007/978-1-60327-489-0_12

Cited by 6 publications

(3 citation statements)

References 119 publications

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“…The heterogeneity of ASD symptoms most likely results from the involvement of a multitude of genetic factors and a complex interaction between those genes and environmental challenges [48][49][50][51][52][53] . For example, increasing evidence suggests a role for inflammation in ASD pathogenesis [54][55][56] .…”

Section: Discussionmentioning

confidence: 99%

Inhibition of TRPV4 rescues circuit and social deficits unmasked by acute inflammatory response in a Shank3 mouse model of Autism

Tzanoulinou

Musardo

Contestabile

et al. 2021

Preprint

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Autism spectrum disorder is a neurodevelopmental disease characterized by social deficits and repetitive behaviors. The high heterogeneity of the disease may be explained by gene and environmental interactions and potential risk factors include immune dysfunctions and immune-mediated co-morbidities. Mutations in the SHANK3 gene have been recognized as a genetic risk factor for ASD. While heterozygous SHANK3 mutations are usually the types of mutations associated with idiopathic autism in patients, heterozygous deletion of Shank3 gene in mice does not commonly induce ASD-related behavioural deficit. Here, we used in-vivo and ex-vivo approaches to demonstrate that region-specific neonatal downregulation of Shank3 in the NAc promotes D1R-MSN hyperexcitability and upregulates Trpv4 to impair social behaviour. Interestingly, genetically vulnerable Shank3+/- mice, when challenged with Lipopolysaccharide to induce inflammatory response, showed similar circuit and behavioural alterations that were rescued by acute Trpv4 inhibition. Altogether our data demonstrate shared molecular and circuit mechanisms between ASD-relevant genetic alterations and environmental insults, which ultimately lead to sociability dysfunctions.

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Section: Discussionmentioning

confidence: 99%

Inhibition of TRPV4 rescues circuit and social deficits unmasked by acute inflammatory response in a Shank3 mouse model of Autism

Tzanoulinou

Musardo

Contestabile

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…It is characterized by marked phenotypic heterogeneity, a fact that is underlined by its broad diagnostic features and by the concept that autism should be viewed not as a single entity with a single cause, 3 but rather as “the autisms.” 1 This clinical variability underlies the challenge facing families and researchers alike—autism spectrum disorders pathogenesis remains a mystery 4 . Proposed pathogenetic mechanisms include aberrant cerebral growth secondary to abnormal neuronal apoptosis and/or synaptic pruning, 5 brain cortex minicolumnar abnormalities, 6 a dysregulated or abnormal immune response, 7 and brain underconnectivity 1 . It seems likely that the various phenotypes may implicate different mechanisms affecting specific cerebral regions, 3 and may be the end result of an interaction of genetic, environmental, neurobiological, and immunological factors 7 …”

Section: Introductionmentioning

confidence: 99%

“…Proposed pathogenetic mechanisms include aberrant cerebral growth secondary to abnormal neuronal apoptosis and/or synaptic pruning, 5 brain cortex minicolumnar abnormalities, 6 a dysregulated or abnormal immune response, 7 and brain underconnectivity 1 . It seems likely that the various phenotypes may implicate different mechanisms affecting specific cerebral regions, 3 and may be the end result of an interaction of genetic, environmental, neurobiological, and immunological factors 7 …”

Section: Introductionmentioning

confidence: 99%