Fluoride affects memory by altering the transcriptional activity in the central nervous system of Lymnaea stagnalis

Fluoride (F^-), has been found to affect learning and memory in several species. In this study, we exposed an F^--naïve, inbred strain of Lymnaea stagnalis to a concentration of F^- similar to that naturally occurring in wild ponds. We found that the exposure to F^- before the configural learning procedure obstructs the memory formation and blocks the configural learning-induced upregulation of CREB1, GRIN1, and HSP70 in snails' central ring ganglia. Along with altering the mRNA levels of these key genes for memory formation, a single acute F^- exposure also upregulates Cytochrome c Oxidase, a major regulatory enzyme of the electron transport chain, which plays direct or indirect roles in reactive oxygen species production. As the central nervous system is sensitive to oxidative stress and consistent with previous studies from mammals, our results suggest a potential role of oxidative stress in memory impairment. To our knowledge, this is the first study investigating the neuronal mechanism of memory impairment in an invertebrate species that is exposed to natural F^- levels.