Fasudil attenuates fluoride-induced neuronal synaptic damage by inhibiting microglial inflammation.

Exposure to high levels of fluoride in drinking water has been linked to cognitive impairment, but the molecular mechanisms underlying this neurotoxicity are not fully understood. In this study, a subchronic rat model was used to investigate whether fluoride-induced synaptic damage involves RhoA/ROCK pathway-mediated microglial activation and inflammation. The role of fasudil, a specific RhoA/ROCK inhibitor, was also evaluated. The results demonstrated that fluoride activated the RhoA/ROCK cascade, stimulated microglial activation and subsequent release of pro-inflammatory cytokines, and resulted in hippocampal synaptic injury. Conversely, fasudil attenuated these effects by downregulating Iba1, TNF-α, and ROCK2 expression. Taken together, these findings establish that RhoA/ROCK signaling critically mediates fluoride-induced neuroinflammation and synaptic damage, thereby offering a mechanistic basis for assessing the neurotoxic risk of environmental fluoride exposure.