Resveratrol regulates Thoc5 to improve maternal immune activation-induced autism-like behaviors in adult mouse offspring.

Maternal infection during pregnancy is an important cause of autism spectrum disorder (ASD) in offspring, and inflammatory infiltration caused by maternal immune activation (MIA) can cause neurodevelopmental disorders in the fetus. Medicine food homologous (MFH) refers to a traditional Chinese medicine (TCM) concept, which effectively combines food functions and medicinal effects. However, no previous study has screened, predicted, and validated the potential targets of MFH herbs for treating ASD. Therefore, in this study, we used comprehensive bioinformatics methods to screen and analyze MFH herbs and drug targets on a large scale, and identified resveratrol and Thoc5 as the best small molecular ingredient and drug target, respectively, for the treatment of MIA-induced ASD. Additionally, the results of in vitro experiments revealed that resveratrol increased the expression of Thoc5 and effectively inhibited lipopolysaccharide-induced inflammatory factor production by BV2 cells. Moreover, in vivo, resveratrol increased the expression of Thoc5 and effectively inhibited placental and fetal brain inflammation in MIA pregnancy mice, and improved ASD-like behaviors in offspring.

Yigansan ameliorates maternal immune activation-induced autism-like behaviours by regulating the IL-17A/TRAF6/MMP9 pathway: Network analysis and experimental validation.

BACKGROUND: Maternal immune activation (MIA) is a significant factor inducing to autism spectrum disorder (ASD) in offspring. The fundamental principle underlying MIA is that inflammation during pregnancy impedes fetal brain development and triggers behavioural alterations in offspring. The intricate pathogenesis of ASD renders drug treatment effects unsatisfactory. Traditional Chinese medicine has strong potential due to its multiple therapeutic targets. Yigansan, composed of seven herbs, is one of the few that has been proven to be effective in treating neuro-psychiatric disorders among numerous traditional Chinese medicine compounds, but its therapeutic effect on ASD remains unknown. HYPOTHESIS: Yigansan improves MIA-induced ASD-like behaviours in offspring by regulating the IL-17 signalling pathway. METHODS: Pregnant C57BL/6J mice were intraperitoneally injected with poly(I:C) to construct MIA models and offspring ASD models. Network analysis identified that the IL-17A/TRAF6/MMP9 pathway is a crucial pathway, and molecular docking confirmed the binding affinity between the monomer of Yigansan and target proteins. qRT-PCR and Western blot were used to detect the expression levels of inflammatory factors and pathway proteins, immunofluorescence was used to detect the distribution of IL-17A, and behavioural tests were used to evaluate the ASD-like behaviours of offspring. RESULTS: We demonstrated that Yigansan can effectively alleviate MIA-induced neuroinflammation of adult offspring by regulating the IL-17A/TRAF6/MMP9 pathway, and the expression of IL-17A was reduced in the prefrontal cortex. Importantly, ASD-like behaviours have been significantly improved. Moreover, we identified that quercetin is the effective monomer for Yigansan to exert therapeutic effects. CONCLUSION: Overall, this study was firstly to corroborate the positive therapeutic effect of Yigansan in the treatment of ASD. We elucidated the relevant molecular mechanism and regulatory pathway involved, determined the optimal therapeutic dose and effective monomer, providing new solutions for the challenges of drug therapy for ASD.

The association between NCAM1 levels and behavioral phenotypes in children with autism spectrum disorder.

Autism spectrum disorders (ASDs) are neuropsychiatric disorders associated with synaptic function and plasticity. Neural cell adhesion molecule (NCAM1) dysfunction impairs synapse formation, synaptic activity and plasticity. To explore the relationship between NCAM1 and ASD, a case-control study was conducted. This research included 40 ASD children and 39 healthy children aged 2-6 years old. We measured the levels of plasma NCAM1 in ASD and healthy control groups by ELISA kits. The severity and behavioral problems of autistic children were also examined. The level of plasma NCAM1 in ASD children was significantly lower than that in controls (p < 0.05). Additionally, NCAM1 levels were negatively correlated with social motivation, social communication and the total scores assessed by Social Responsiveness Scale (SRS). NCAM1 levels positively correlated with gross motor ability and developmental quotient in the ASD group. The area under the ROC curve of NCAM1 was 0.647. These results indicated that NCAM1 levels are associated with behavioral problems in children with ASD. These include phenotypes relating to social motivation, social communication, gross motor ability and developmental quotient. These results suggest that future studies exploring the function of NCAM1 in the context of etiology of ASD may be needed.

Study on the characteristics of auditory in children with autism spectrum disorders / 中国学校卫生

Objective@#To explore the characteristics of Auditory Brainstem Response (ABR) in children with ASD, and analyze their relation with the core symptoms of ASD.@*Methods@#Ninty children aged 2-6 with ASD were recruited from Harbin in this study. The data of ABR was collected by using BAEP, and the association among children’s absolute latency and interpeak latency of ABR, core symptoms of ASD children’s behavior and clinical manifestation was analyzed.@*Results@#Compared with the normal average value, children with ASD had longer the absolute latency of wave Ⅰ,Ⅲ,Ⅴ in bilateral ears, which were (1.51±0.20)(3.83±0.34)(5.63±0.23)ms, (1.54±0.16) (3.78±0.23) (5.63±0.22)ms, respectively(P<0.05). Some children’s interpeak latency of Ⅰ-Ⅲ, Ⅲ-Ⅴ, Ⅰ-Ⅴ were longer than normal values. Children younger than 3 years old showed prolonged peak intervals of Ⅰ-Ⅲ and Ⅰ-Ⅴ than children in 3-7 years old. The study has also showed that there was positive correlation between the absolute latency of waveⅠin left ear and the social function defect(r=0.45, P<0.05); there was positive correlation between the latency of wave Ⅴin right ear or the latency of waveⅠin left ear or the Ⅰ-Ⅲ peakinterval and nonverbal communication ability dysfunction(r=0.35, 0.39, 0.34, P<0.05); there was positive correlation between the Ⅰ-Ⅲ peak interval and the repeated stereotyped symptoms(r=0.39, 0.35, P<0.05).@*Conclusion@#Children with ASD have abnormal auditory behavior. The absolute latency and interpeak latency of ABR is correlated to some parts of core symptoms of ASD.

Case-control study on temperament characteristics of children with autism spectrum disorders aged 3-7 years old in Harbin / 中国学校卫生

Objective@#To explore the differences of temperament characteristics between children with autism spectrum disorder (ASD) and normal children, and to provide evidence for early detection of ASD children and the development of personalized treatment plans.@*Methods@#In this case-control study, we enrolled 129 ASD children and 129 normal children aged 3-7 years. The Behavioral Style Questionnaire (BSQ) scale was used to assess the temperament.@*Results@#ASD children got higher scores in terms of "activity level", "withdrawal", "adaptability", "emotional nature", "persistence", and "response threshold" temperament dimensionality scores(P<0.05), and lower scores in terms of "rhythmical", "response intensity" temperament dimensionality scores than normal children(P<0.05). However, there was no significant difference in "attention dispersiveness" between ASD group and control group(P>0.05). Among the children in the ASD and control group, the proportion of each temperament type was "easy to raise temperament type" (41.8% vs 62.8%), "partially easy to raise temperament type" (31.8% vs 27.9%), "partially difficult to raise temperament type" (17.1% vs 6.2%), “slow-up-towarm temperament type" (7.7% vs 2.3%) and "difficult to raise temperament type" (1.6% vs 0.8%).Statistical analysis showed that the rate of "easy to raise temperament type" was lower than that in normal children(P<0.05), while the rates of "partially easy to raise temperament type", "partially difficult to raise temperament type", "difficult to raise temperament type", and "slow-up-to-warm temperament type" in ASD children were higher(P<0.05).@*Conclusion@#There was significant difference in temperament characteristics between ASD children and normal children. The evaluation of temperament type contributes to early detection of ASD children and provides a reference for their behavioral correction.