Oral doxycycline increases microglia numbers in the mouse hippocampus

Exposure to indoor mold causes deficits in learning and memory, however the neural mechanisms for these effects have not been established. Earlier work from our labs using a mouse model determined that exposure to the mold Stachybotrys resulted in central inflammation, decreased survival of newly formed hippocampal neurons, and impaired hippocampal-dependent memory. Here we treated mold-exposed animals with a doxycycline diet (DD) to determine whether antibiotic treatment would mitigate the effects of mold exposure. Adult male C57Bl/6 mice were given intact mold spores (IN) intranasally or saline vehicle (VEH) 3x/week for 4 weeks. Half of the IN and VEH animals received doxycycline in their diet (DD). All mice were injected with BrdU 31–37 days prior to sacrifice. We quantified BrdU+/NeuN+ new neurons and iba1-expressing cells within the dorsomedial dentate gyrus. The latter were characterized as ramified, primed, ameboid, rod-like, migratory or monocyte-like. DD increased Iba1+ cells overall, and also ramified cells specifically, in both VEH and IN groups. IN increased monocyte-like cells, which were not attenuated by DD. Interestingly, numbers of migratory microglial cells were positively correlated with numbers of mature new neurons in the subgranular zone across treatment groups, suggesting a potential neuroprotective role for this microglial phenotype. In sum, DD increased numbers of microglial cells in the dentate gyrus but did not prevent infiltration of monocyte-like cells.