An international collaborative research group led by Professor Toru Uchitaku of Kobe University Graduate School found that the cause of idiopathic autism is an epigenetic (Note) abnormality of hematopoietic cells during the fetus, and the results can be seen in the brain and intestines. It was revealed that it was an immune disorder.
Immune disorders are now the cause of various diseases and play an important role in the development of autism.Inflammation in the brain and disorders of the peripheral immune system are frequently observed in patients with autism.Furthermore, immune abnormalities are associated with abnormalities in the intestinal bacterial flora, and are thought to be involved in the onset due to the connection between the brain and the intestine (cerebral intestinal axis).However, the mechanism behind these immune disorders was unknown.
Considering the important developmental stages of immune disorders and the widespread involvement of the immune system in the development of autism, the researchers hypothesized that a common etiology underlies widespread immune dysregulation and lies in different types of progenitor cells. ..We focused on the hematopoietic cells that form the basis of immune cells, and focused on the yolk sac (YS) and the aorta-gonad-mesonephros (AGM), which are involved in hematopoiesis during fetal life.
The research group analyzed AGM blood cell lineage cells using BTBR mice, an autism model animal, and identified HDAC1 (histone deacetylase 1) as the etiology of immune disorders.In addition, HDAC1 was also identified as the etiology of microglial (one of the central nervous system glia cells responsible for central immunity) developmental abnormalities by analysis of YS blood cell lineage cells.In fact, by regulating HDAC activity (administering HDACXNUMX inhibitor) during the fetal period, intracerebral inflammation and immune dysregulation in mice were ameliorated.Furthermore, it was found that changes in the intestinal environment, especially the immune system, cause abnormalities in the intestinal flora of mice.
In the future, it is expected that new treatment strategies for autism and other neurodevelopmental disorders will be created as the pathological classification of autism progresses.
Note: Even if the base sequence of DNA is the same, the inheritance pattern in which gene expression differs due to the modification of DNA with a chemical substance.
Paper information:[Molecular Psychiatry] A common epigenetic mechanism across different cellular origins underlies systemic immune dysregulation in an idiopathic autism mouse model