Contribution of microglia to daily and regional differences in excitotoxic susceptibility.

Microglial can be neuroprotective or neurodamaging. We previously identified regional and time-of-day differences in ex vivo excitotoxicity, with the suprachiasmatic nucleus (SCN) more resilient than the anterior hypothalamus (AH) and cortex, and with all three regions more vulnerable at night. Here we investigated whether microglia contribute to these differences. First, we compared microglia between slices acutely fixed at different times of day vs. slices maintained ex vivo. Next, we investigated microglial changes in cortex and SCN/AH ex vivo slices in response to excitotoxic treatment at different times of day. Lastly, we investigated whether minocycline alters excitotoxicity-induced microglial changes and cell damage in ex vivo cortex slices. Acute slices exhibit regional and time-of-day differences in microglia morphology and density, with few differences compared to ex vivo brain slices. In ex vivo tissues, microglial density is higher, and excitotoxicity induces more changes in the cortex compared to the SCN and AH. Also, microglial density is higher and may exhibit more complex morphology in cortex slices under excitotoxic conditions in the daytime. Finally, minocycline decreases NMDA-induced cell death at night but not during the day in cortex slices. Together, these data support microglia contributing to regional and daily rhythms in excitotoxic susceptibility.