Retinoic acid administration normalizes aberrant microglial activation via regulating TREM2 transcription in the PFC of valproic acid induced autism rat.

Scientists studied rats with autism-like behaviors and found problems with brain immune cells called microglia. When they gave these rats retinoic acid (a form of vitamin A), the rats showed improved behaviors and healthier brain immune responses. The study suggests that vitamin A deficiency might contribute to autism symptoms by affecting brain immune function, and that vitamin A supplementation could potentially help.

This animal study investigated the role of retinoic acid (RA) in autism-like behaviors using valproic acid (VPA)-induced autism rats. Researchers found that VPA rats showed disrupted RA signaling and increased microglial activation (brain immune cell dysfunction). When RA was administered to these rats, it improved autism-like behaviors and normalized microglial function. The study identified that RA works through the RARα-TREM2 pathway, where RA increases RARα expression, which then regulates TREM2 gene transcription to control microglial activation.

The research suggests that disrupted RA signaling and abnormal brain immune responses may contribute to autism development, and that RA supplementation could potentially address these issues through specific molecular mechanisms.

Results suggest vitamin A supplementation might benefit some autistic individuals by improving brain immune function. However, human studies are needed before clinical recommendations. Healthcare providers should monitor vitamin A status in autistic patients and consider supplementation if deficient.

Animal study using VPA-induced autism model may not fully represent human autism. Sample size not reported. Single study requiring replication. Unclear if findings translate to naturally occurring autism in humans.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disease with an unclear underlying pathogenesis. Disruption of retinoic acid (RA)-retinoic acid receptor α (RARα) signaling and aberrant microglial activation were reported to be involved in the pathogenesis of ASD. However, the effect of RA-RARα signaling on microglial activation in ASD and the underlying mechanisms are unknown. Herein, we found inhibited RA-RARα signaling and increased microglial activation in valproic acid (VPA)-induced autism rats.

Furthermore, we administered RA to VPA rats and found that RA ameliorated autism-like behaviors, inhibited microglial activation and normalized microglial polarization in VPA rats. Additionally, the expression levels of RARα and triggering receptor expressed on myeloid cells 2 (TREM2) were increased in the prefrontal cortex (PFC) of VPA rats given RA. Chromatin immunoprecipitation (ChIP) and dual luciferase reporter assays confirmed that RARα can regulate the transcriptional activity of the TREM2 gene by binding to its promoter. We conclude that RA administration ameliorates autism-like behaviors in VPA rats by inhibiting microglial activation and normalizing microglial polarization through the regulation of TREM2 transcription by RARα.