Olfactory bulb microglia activation mediates neuronal pyroptosis in ozone-exposed mice with olfactory and cognitive dysfunction.

In recent years, there has been a notable increase in the concentration of air pollutants in the troposphere, especially ozone. However, limited research has gone beyond examining histopathological alterations in the olfactory bulb (OB) to explore the effects of ozone exposure on olfactory and cognitive functions. In our study, we exposed nine-month-old C57BL/6 mice to ozone at a concentration of 1.0 ppm for 13 weeks to examine the effects of ozone on the OB. The results indicated that ozone exposure induces olfactory and cognitive impairments in the mice. Subsequently, microglia in the OB are activated, leading to neuroinflammation. Ozone-induced downregulation of PSD95 and Synaptophysin, which was accompanied by a decrease in dendritic length and spine density. Simultaneously, increasing in the co-labeling of C1q, Iba1, and PSD95 after ozone exposure indicated that C1q-mediated synaptic phagocytosis by microglia might play a role in synaptic damage. Furthermore, the co-labeling of GSDMD-N and NEUN results suggests that ozone exposure triggers pyroptosis in neurons. Additionally, minocycline administration can alleviate ozone-induced olfactory and cognitive impairments by suppressing microglial activation. This study illustrates that prolonged ozone exposure leads to microglial activation in the OB, causing synaptic damage, neuronal pyroptosis, and subsequent deficits in olfactory and cognitive functions.