INVESTIGATING DIFFERENTIAL EXCITOTOXIC SUSCEPTIBILITY ACROSS BRAIN REGIONS

Various pathological conditions generate excitotoxic conditions resulting in cell death. We have found that the suprachiasmatic nucleus (SCN) is more resistant to excitotoxic damage compared to the anterior hypothalamus (AH) and cortex. We have also found time-of-day differences in excitotoxic susceptibility in all three regions. Given that excitotoxic stimuli induce changes in microglia activity, we are investigating whether differences in microglial responses may contribute to the SCN’s excitotoxic resiliency and to the day-night susceptibility differences we have observed. Observations have revealed that the microglia cell in the cortex are more sensitive to changes in microglial activity as shown by the shift in morphology compared to SCN and AH. Additionally, there are time-of-day differences in the microglial activity in the different brain areas in terms of microglial morphology and expression of pro-inflammatory and anti-inflammatory cell surface markers. To a certain extent, these differences can explain the time of day we observe in resiliency and susceptibility in different brain areas.