Endogenous retrovirus-derived RNA-DNA hybrids induce microglial synaptic pruning in autism models - PubMed
4 hours ago
- #ERV
- #autism
- #microglia
- Microglia-mediated neuroinflammation is a key component in autism spectrum disorders (ASDs).
- Deficiency in the ASD gene SETDB1 and maternal immune activation (MIA) increase C4b expression in prefrontal cortex neurons.
- Elevated C4b triggers excessive microglial synaptic pruning, leading to autistic-like behaviors.
- Microglia elimination improves synaptic density, and C4b knockout rescues autistic-like phenotypes in mice.
- C4b expression is driven by RNA-DNA hybrids from reactivated endogenous retroviruses (ERVs).
- FDA-approved HIV medications that inhibit retrotranscriptional activity reduce C4b levels and alleviate ASD symptoms.
- Targeting ERV reactivation with HIV medications shows therapeutic potential for ASD.