Behavioral effects of chronic PFHxA exposure on spatial memory function.

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants widely detected in human biological samples. As regulatory restrictions on long-chain PFAS such as PFOA and PFOS have increased, short-chain alternatives, including perfluorohexanoic acid (PFHxA) have been widely adopted due to their lower bioaccumulation potential. However, their potential neurodevelopmental effects remain poorly understood. In this study, we investigated the long-term behavioral and neurobiological consequences of chronic PFHxA exposure beginning during the neurodevelopmental period and continuing throughout the lifespan. Behavioral assessments revealed that PFHxA exposure selectively impaired spatial memory. In both the novel object recognition and object location tests, PFHxA-exposed mice failed to show a significant preference for novel or relocated objects, indicating deficits in recognition and spatial memory. In contrast, no significant differences were observed in long-term memory, motor function, or social behaviors. Collectively, these findings suggest that chronic PFHxA exposure may induce subtle cognitive alterations and highlight the potential neurodevelopmental hazard of this short-chain PFAS.