(p=9.5e-08), and for tesa treatment in the PFC (p=3.09e-05). This is consistent with the activity of tesa at PPARγ (Table S6). ORA of the Searcy dataset did not support an overall pioglitazone-mediated suppression of inflammatory processes, which is consistent with our findings. Additionally, their dataset and ours both exhibit alterations in genes involved in glutamatergic signaling. Functional studies further support a role for PPPAR agonists in glutamatergic signaling. For example, pioglitazone reduced NMDA-mediated calcium currents in brain38, and the antidepressant effects of pioglitazone (mentioned above) were enhanced by co-administration of MK-801, an NMDA receptor blocker, and reversed by administration of NMDA 52. Moreover, the partial rescue of scopolamine-induced memory impairment by pioglitazone in mice was decreased by sub-effective doses of MK-801 and increased by NMDA3.
