Autism Spectrum Disorders (ASDs) are reported as a group of neurodevelopmental disorders. The structural changes of brain regions including the hippocampus were widely reported in autistic patients and mouse models with dysfunction of ASD risk genes, but the underlying mechanisms are not fully understood. Here, we report that deletion of Trio, a high-susceptibility gene of ASDs, causes a postnatal dentate gyrus (DG) hypoplasia with a zigzagged suprapyramidal blade, and the Trio-deficient mice display autism-like behaviors. The impaired morphogenesis of DG is mainly caused by disturbing the postnatal distribution of postmitotic granule cells (GCs), which further results in a migration deficit of neural progenitors. Furthermore, we reveal that Trio plays different roles in various excitatory neural cells by spatial transcriptomic sequencing, especially the role of regulating the migration of postmitotic GCs. In summary, our findings provide evidence of cellular mechanisms that Trio is involved in postnatal DG morphogenesis.
Animals ; Dentate Gyrus/metabolism* ; Mice ; Morphogenesis/physiology* ; Neurons/pathology* ; Cell Movement ; Mice, Inbred C57BL ; Autism Spectrum Disorder/pathology* ; Mice, Knockout ; Neural Stem Cells ; Male ; Neurogenesis ; Autistic Disorder/genetics*

The term “particulate Matter (PM)” refers to the mixture of small-sized solid particles and liquid droplets floating in the air, and is referred to as PM₁₀ ( < 10 µm), PM(2.5) ( < 2.5 µm) and PM(1.0). Much PM is an anthropogenic substance generated by transportation or industrial activities, which is transformed into a second toxic substance by chemical reactions in the atmosphere. PM reaches the brain directly through olfactory transport, or through the blood-brain barrier during systemic circulation. PM that enters the local cerebral circulation causes neuroinflammation through microglial cells and endotoxins. According to previous studies, greater PM exposure results in lower brain volume, especially white matter. Among neurodevelopmental disorders, the correlation between the occurrence of autism spectrum disorder and exposure to PM is widely known. Other studies have found that exposure to PM was associated with low cognitive function and increased rate of cognitive aging. PM can also cause pathology of early Alzheimer's disease and increases the risk of Alzheimer's dementia and mild cognitive impairment.
Air Pollution ; Alzheimer Disease ; Atmosphere ; Autism Spectrum Disorder ; Blood-Brain Barrier ; Brain ; Cerebrovascular Circulation ; Cognition ; Cognitive Aging ; Dementia ; Endotoxins ; Mild Cognitive Impairment ; Neurodevelopmental Disorders ; Particulate Matter ; Pathology ; Transportation ; White Matter

Autism spectrum disorder (ASD) is characterized by persistent deficits within two core symptom domains: social communication and restricted, repetitive behaviors. Although numerous studies have reported psychopharmacological treatment outcomes for the core symptom domains of ASD, there are not enough studies on fundamental treatments based on the etiological pathology of ASD. Studies on candidate medications related to the pathogenesis of ASD, such as naltrexone and secretin, were conducted, but the results were inconclusive. Oxytocin has been identified as having an important role in maternal behavior and attachment, and it has been recognized as a key factor in the social developmental deficit seen in ASD. Genetic studies have also identified associations between ASD and the oxytocin pathway. As ASD has its onset in infancy, parents are willing to try even experimental or unapproved treatments in an effort to avoid missing the critical period for diagnosis and treatment, which can place their child in an irreversible state. While therapeutic application of oxytocin for ASD is in its early stages, we have concluded that oxytocin would be a promising therapeutic substance via a thorough literature review focusing on the following: the relationship between oxytocin and sociality; single nucleotide polymorphisms as a biological marker of ASD; and validity verification of oxytocin treatment in humans. We also reviewed materials related to the mechanism of oxytocin action that may support its potential application in treating ASD.
Autistic Disorder* ; Child ; Autism Spectrum Disorder* ; Critical Period (Psychology) ; Diagnosis ; Humans ; Maternal Behavior ; Naltrexone ; Oxytocin* ; Parents ; Pathology ; Polymorphism, Single Nucleotide ; Secretin ; Social Change ; Biomarkers