| Autism is also called autism spectrum disorder (ASD).
The above research results were completed by the research group of Zhou Zikai, a researcher at the Shanghai Mental Health Center-Shanghai Institute of Materia Medica, Chinese Academy of Sciences, and Ji Minjun, a professor at the State Key Laboratory of Reproductive Medicine and Department of Pathogen Biology, Nanjing Medical University.
Simulate a "more real" pathogenic mechanism
Simulate a "more real" pathogenic mechanism ASD is considered to be a neurodevelopmental disorder characterized by social communication disorders, repetitive stereotyped behaviors and narrow interests.
To clarify the pathogenic mechanism of ASD is an important goal of related scientific research and is of great significance to clinical treatment.
The biological research on ASD mainly revolves around classic experimental animal models.
The research team chose an animal model of MIA.
"Almost all immune activators used in related studies are virus infection mimic polyinosinic acid poly(I:C) and bacterial infection mimic lipopolysaccharide LPS.
Therefore, it is urgent to establish a new disease model and reveal its simulated "more real" pathogenic mechanism.
For this reason, the researchers used the Toxoplasma gondii tachyzoite soluble complex antigen (STAg), which infects one third of the world’s population, to induce MIA and establish a mouse model with immune abnormalities and autism phenotypes in the offspring.
"STAg is a mixture of macromolecules, which can effectively activate the immune system, while avoiding the impact of the vertical transmission of living pathogens from the mother to the offspring on the evaluation of the MIA effect.
Zhou Zikai further added that the important thing is that the model can better simulate the pathological process and mechanism, and has a high structural validity.
Sustainable into adulthood
Sustainable into adulthood Existing epidemiological and laboratory animal research results show that MIA caused by pathogens from the mother during pregnancy is one of the risk factors that induce autism in the offspring; at the same time, MIA can have a lasting impact on the peripheral and central immune systems of the offspring , May be the cause of some immune abnormal autism.
The research team further confirmed by studying the above-mentioned new experimental animal models that the offspring of sick mice have abnormal peripheral and central immune lineages until they reach adulthood, and found that their T cell profile characteristics are consistent with those of some autistic patients; and that sick mice have social interaction defects, The core symptom of autism with repetitive stereotyped movements and communication disorders.
"The specific manifestations are the imbalance of the proportion of CD4 + T cell subsets and the high expression of IL-6 factor mediated by astrocytes in the brain, which persists into adulthood.
+ In addition, there are irreversible abnormal changes in the white matter microstructure of adult mice.
Activated mouse regulatory T cells are effective
Activated mouse regulatory T cells are effective At present, the recognized core symptoms of ASD are social interaction defects, repetitive stereotyped movements, and communication disorders.
Li Yamin, a professor at the Second Xiangya Hospital of Central South University, and others once wrote that only risperidone and aripiprazole are approved to treat irritability in children with ASD.
There is still a lack of clinical drugs for the treatment of core symptoms of ASD, and the efficacy of each drug is controversial.
, Its long-term effectiveness and safety need more clinical studies to demonstrate.
In the research of the disease model adopted by the research team, the peripheral immunity and central nervous immunity of the sick mice were analyzed and screened systematically and comprehensively.
The results showed that the proportion of CD4 + T cell subsets was dysregulated, including a significant decrease in the proportion of regulatory T cells (Treg).
+ Treg cells play a key role in maintaining immune balance has been recognized by the academic community.
"We tried adoptive infusion of highly active Treg, and found that although the improvement of the abnormal microstructure of the white matter fibers of the diseased mouse is relatively limited, it can effectively reverse most of the immunological and behavioral phenotypes.
" Zhou Zikai said.
Further research found that by comparing the transcriptomes of Treg cells from different sources by single-cell sequencing technology, the researchers identified a group of high-efficiency Treg cell subsets and their transcriptomic characteristics.
Such high-efficiency Treg cells are better It works by moving into the brain area associated with disease symptoms.
Based on the results of this study, the regulatory T cell drugs engineered by the research team based on the molecular characteristics of high-efficiency cell subsets are expected to improve the core symptoms of immune abnormal autism and provide new ideas for subsequent clinical translational research.
(Source: Qin Zhiwei, China Science News)
Related paper information: org/10.
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1038/s41593-021-00837-1
org/10.
1038/s41593-021-00837-1" target="_blank">https://doi.
org/10.
1038/s41593-021-00837-1
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