摘要Background:Maternal viral infection during pregnancy can lead to maternal immune activation(MIA),increasing the risk of neurodevelopmental disorders in offspring.Amantadine(AMA)exhibits antiviral activity and is widely employed in the manage-ment of neurologic conditions.Nevertheless,the efficacy of AMA in treating MIA is currently not established.Methods:MIA was induced by polyinosinic acid-polycytidylic acid(poly(I:C));AMA was administered from embryonic(E)day 11.5 for 3days.BV-2 cells were stimulated using poly(I:C)and treated with AMA.Behavior was assessed via open field test,elevated plus maze test,three-chamber sociability test,and marble burying test.Neuronal morphology was vizualized using Nissl stain;apoptosis via TUNEL(terminal deoxynucleotidyl transferase dUTP nick-end labeling)stain;protein expression(Iba1,NeuN,CD68,TNF-α[tumor necrosis factor-alpha],IL-1β[interleukin-1β])using immu-nofluorescence(IF);interleukin-6(IL-6)levels using enzyme-linked immunosorbent assay;reactive oxygen species using staining;Iba1,NeuN,Bcl-2,Bax,and cleaved caspase 3 using Western blot;and gene expression changes using RNA-seq.Results:AMA treatment reduced the levels of IL-6 in maternal blood,improved autism-like behaviors in MIA offspring,and effectively prevented neuronal damage and neuroinflammation.In vitro cellular studies have demonstrated that AMA effec-tively downregulates the expression levels of pro-inflammatory cytokines,including IL-6,TNF-α,and IL-1β.RNA-seq analysis indicated that AMA mitigates abnormal acti-vation of microglia by modulating inflammatory pathways associated with IL-6.Conclusion:AMA can prevent the development of neuropsychiatric disorders in MIA offspring.This effect may be related to its ability to attenuate neuronal damage,re-duce neuronal apoptosis,and inhibit neuroinflammation,indicating that the antiviral drug AMA may be a potential treatment for MIA.