Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants widely detected in human biological samples. These substances have been increasingly recognized as pollutants in marine ecosystems. 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. While these short-chain alternatives readily disperse across marine ecosystems due to their high aqueous solubility and environmental mobility, 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 short-term 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 risk of this short-chain PFAS.
 

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