Iron Deficiency Affects Seizure Susceptibility in a Time- and Sex-Specific Manner

Abstract

Iron deficiency (ID) affects more than three billion people worldwide making it the most common micronutrient deficiency. ID is most prevalent during gestation and early life, which is of particular concern since its impact on the developing central nervous system is associated with an increased risk of a wide range of different psychiatric disorders later in life. The cause for this association is not known, but many of these same disorders are also associated with an imbalance between excitation and inhibition (E/I) within the brain. Based on this shared impairment, we asked whether ID could contribute to such an imbalance. Disruptions in the E/I balance can be uncovered by the brain’s response to seizure inducing insults. We therefore tested the seizure threshold under different nutritional models of ID. We found that mice which were postnatally exposed to ID (and were acutely ID) had a decreased seizure threshold and increased susceptibility to certain seizure types. In contrast, mice that were exposed to ID only during gestation had an increased seizure threshold and low seizure incidence. We suggest that exposure to ID during gestation might alter the cellular components that contribute to the establishment of a proper E/I balance later in life. In addition, our data highlight the importance of considering the window of vulnerability since gestational ID and postnatal ID have significantly different consequences on seizure probability.