Hypoxia Alters miRNAs Levels Involved in Non-Mendelian Inheritance of Autism Spectrum Disorder in Mice.

Scientists studied how low oxygen levels during birth affect mouse brain development. They found that oxygen deprivation caused brain damage and changed the expression of genes linked to autism. The mice showed autism-like behaviors including less social interaction and repetitive movements. Even mild oxygen deprivation had effects, but severe cases were worse. This suggests that birth complications involving low oxygen might increase autism risk.

This mouse study investigated how neonatal hypoxia (oxygen deprivation) affects brain development and autism-related behaviors. Researchers exposed newborn mice to varying oxygen levels (8%, 10%, 12%) and found dose-dependent effects. Hypoxia increased brain cell death markers in the cortex and hippocampus, altered expression of autism-associated microRNAs (miR-19a-3p, miR-361-5p, miR-150-5p, miR-126-3p, miR-499a-5p), and caused behavioral changes including reduced social interaction, repetitive behaviors, and corner-seeking. Effects were detectable even with mild hypoxia (12% oxygen) but most pronounced with severe hypoxia (8-10% oxygen).

The study suggests neonatal hypoxia may contribute to autism-like phenotypes through epigenetic mechanisms involving microRNA dysregulation.

Results suggest neonatal hypoxia may contribute to autism risk through epigenetic mechanisms. Early detection and intervention for newborns with hypoxia exposure may be important. Findings support investigating perinatal complications as autism risk factors and developing neuroprotective strategies for at-risk infants.

Study conducted only in mice, limiting direct applicability to humans. Sample size not reported. Long-term behavioral outcomes unclear. Causality between microRNA changes and behavioral phenotypes not established. No comparison to human perinatal hypoxia data.

Hypoxia can occur to varying degrees for different reasons during the perinatal period, affecting development. We aim to examine the consequences of mild to severe neonatal hypoxia in mice, focusing on its potential link to neurodegenerative fetal brain dysfunctions related to autism spectrum disorder (ASD). We induced hypoxia in neonatal mice by delivering them in controlled environments with varying oxygen concentrations. The results showed elevated levels of HIF-1α (a marker of hypoxia) in the cerebral cortex and hippocampus, as well as increased neurodegeneration in these regions.

Moreover, we observed altered expression of ASD-related miRNAs (miR-19a-3p, miR-361-5p, miR-150-5p, miR-126-3p, and miR-499a-5p) in hypoxic groups, consistent with previous results in human and animal models of ASD. These molecular alterations were accompanied by behavioral changes such as decreased movement, speed, social interaction, and repetitive behaviors, as well as an increased tendency to exhibit corner-seeking behavior in mice subjected to hypoxic conditions. Although behavioral and molecular changes were detectable in the 12% O2 group (mild hypoxia), the most pronounced changes were observed in the more severe hypoxia groups, at 10% O2 and 8% O2. Overall, the results suggest that neonatal hypoxia can induce lasting molecular changes associated with neurodegenerative diseases with behavioral consequences.

Moreover, even in normal birth, exposure to hypoxia during early development can impair memory and learning. The results highlight the need for early detection and intervention in newborns exposed to hypoxia to prevent long-term neurological problems. miRNA levels are regulated during development, and their modifications in tissues, especially in germ cells, constitute a risk factor for the next generation. The analyses provide a basis for studying the regulatory pathways that affect functional and behavioral changes under hypoxia.