Fig. 8.

Under normal physiological conditions, E2 maintains microglial stability, and brain metabolic balance, thereby exerting its neuroprotective effects. The supraphysiological doses of estrogen (sE2) treatment activate the ERα/NF-κB pathway, promote the microglial response and brain metabolic imbalance, and then induce the neuroinflammation-mediated neuronal damage, ultimately resulting in depressive-like behaviors in mice