Pubmed du 27/07/25
1. Kosaki Y, Mihara R. Context blindness in the BTBR T(+) tf mouse model of autism: Impaired contextual control of discrimination reversal learning. Behav Brain Res;2025 (Jul 27):115752.
Behavioural inflexibility-a hallmark of autism spectrum disorder (ASD)-can be characterised by the persistence of established behaviours in inappropriate contexts. This inflexibility may arise from a reduced ability to use contextual information to disambiguate effective contingencies, thereby impeding the flexible expression of instrumental behaviour in a contextually appropriate manner. In this study, we employed the BTBR T(+) tf inbred mouse model of ASD to examine whether contextual control of behaviour is impaired in these mice. BTBR and control C57BL/6J (B6) mice were first trained on a T-maze positional discrimination task, after which they were subjected to a reversal task conducted in either the same or a different maze context. The contextual shift significantly facilitated the acquisition of reversal discrimination in B6 mice, whereas it had no effect on BTBR mice. The lack of contextual control resulted in poorer reversal performance in BTBR in the new context, while both strains performed comparably when the context remained unchanged. A subsequent experiment ruled out the possibility that BTBR mice were simply unable to differentiate between the two maze contexts, as they demonstrated normal differential contextual conditioning. Overall, these findings suggest that BTBR mice are critically impaired in utilising contextual cues to disambiguate the effective stimulus-response-outcome contingencies in a hierarchical manner. This supports the notion that « context blindness » is a core deficit in ASD and warrants further investigation into its neurobiological underpinnings.
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2. Miao Y, Luo R, Lin F, Tong B, Yan J, Yang T, Sun Z, Li T, Xiao L, Chen J. Increasing indoxyl sulfate induces iNOS expression via aryl hydrocarbon receptor leading to microglia hyperactivation in the prefrontal cortex of autism-like offspring rats. Neurosci Lett;2025 (Jul 27);862:138298.
The abnormal indole metabolism is associated with the progression of Autism Spectrum Disorder (ASD). Indoxyl sulfate (IS), one of the active products of indole metabolism, still has an unknown role in ASD progression. This study investigates the role of IS/Aryl hydrocarbon receptor (AhR)/iNOS pathway in microglial activation in the prefrontal cortex (PFC) of ASD-like rats. Prenatal LPS-exposed induced autism-like behaviors offspring rats, concomitant with increased IS levels in the PFC. The levels of nuclear-AhR, IBA1, CD16 and iNOS proteins expression were increased in the PFC of LPS-exposed rats, whereas ARG1 protein expression level decreased, indicates microglia hyperactivation coupled with altered microglia morphology. ELISA analysis and further measure of synapses changes showed significantly increased inflammatory factors (TNF-α and IL-1β) and synaptic alterations. In vitro experiments demonstrated that IS treatment significantly upregulated the expression level of nuclear-AhR, enhanced microglia marker (IBA1, CD16 and iNOS) proteins and pro-inflammation factors levels (TNF-α and IL-1β), while concurrently reducing ARG1 protein expression and IL-10 levels in BV2 microglial cells. Moreover, the IS treatment significantly enhanced AhR enrichment in iNOS promoter region by chromatin immunoprecipitation and dual luciferase reporter assays, thereby significantly elevating the iNOS expression. However, the AhR-specific antagonist CH-223191 could block this activation and reverse the above proteins and inflammation factors changes. In a word, increased IS levels in the PFC of ASD-like offspring rats activate the AhR/iNOS pathway, driving microglial hyperresponsiveness and contributing to the development of ASD disease.
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3. Wong OW, Sm Chan S, Chau SW, Chu WC, Ho CS, Ho SW, Hung SF, Hussain S, Lai KY, Lam AM, Lo HH, Ma KK, Ma SL, Mo FY, Sham PC, Shea CK, So SH, Tsoi KK, Leung PW. Autism epidemiology in Hong Kong children and youths aged 6-17: Implications on autism screening and sex differences in the community. Autism;2025 (Jul 27):13623613251360269.
Epidemiological studies on autism lack representation from Asia. We estimated the prevalence of autism among children and youths in Hong Kong using a two-stage approach. In addition, we evaluated the psychometric properties of the screening instrument and explored sex differences within an epidemiological context. A random school-based sample of 5,865 children and youths were screened with the Autism Spectrum Quotient-10 (AQ-10). Then, a subsample of 317 participants underwent the Autism Diagnostic Interview-Revised assessment. Prevalence was estimated by applying positive and negative predictive values (PPV/NPV) of AQ-10 derived from the subsample to the entire cohort. None of the screened negative participants had autism, resulting in an NPV of 100%. Discrepant PPVs were noted for males (20.4%) and females (5.20%). The estimated prevalence was 2.57% using sex-specific PPVs. Explorative analysis on AQ-10 Positive participants without the diagnosis (i.e. ‘false positives’) showed significantly elevated autistic symptoms. The prevalence of autism in Hong Kong is comparable to the recent estimates in Western countries, which poses a significant public health challenge. Despite the high false-positive rates, AQ-10 remains valuable for excluding autism and identifying those with autistic symptoms. Furthermore, community-based studies are crucial to address sex differences in autism expression.Lay abstractAlthough studies have found that autism is becoming more common, little is known whether this is true in Asian countries. This study looked into how many children and teenagers in Hong Kong might have autism. We first screened 5,865 school-aged children and youths with the Autism Spectrum Quotient-10 (AQ-10). Then, we conducted in-depth interviews with 317 of them to assess for autism. We found that around 2.57% of children and youths aged 6-17 years in Hong Kong might have autism. This number is similar to that of the Western countries. Furthermore, we also discovered that boys who were screened positive on the AQ-10 were more likely to have autism than girls. This could be because autism is more common in boys, and the AQ-10 might be better at spotting autism in boys than in girls. In the future, studies will need to find an optimal way of detecting autism in the community, considering how autism may present differently in boys and girls.
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4. Zhan X, Kuang Z, Wang Y, Li X, Zeng Y, Zhong Y. Health benefits of adapted physical activity for children and adolescents with autism Using the ICF-CY framework: A scoping review. Dev Neurorehabil;2025 (Jul 27):1-14.
PURPOSE: The aim of this study was to conduct a scoping review of the health benefits of adapted physical activity (APA) programs for children and adolescents with autism based on the ICF-CY. METHODS: Retrieving experimental studies related to APA in children and adolescents (0-18 years) with autism in the PubMed, Web of Science, EBSCO, PsycINFO, and CNKI databases, January 2014-December 2023. RESULTS: A total of 34 studies were included (involving 13 countries and 997 subjects). Coding of health effects according to ICF-CY categories, 52% of the 210 outcome items focused on body functions, 48% on activities and participation. CONCLUSIONS: With its individualized, diversified and structured characteristics, APA not only serves as an effective non-pharmacological treatment strategy, but also an important way to promote the health of children and adolescents with autism in all-round way. However, the complexity of environmental factors makes it challenging to design an APA program based on the concept of ICF-CY.
