4-Hydroxy TEMPO Attenuates Dichlorvos InducedMicroglial Activation and Apoptosis

摘要

Microglial cells have been implicated in various neurodegenerative diseases. Previous studies from our lab have shown that dichlorvos (an organophosphate) could induce Parkinson’s like features in rats. Recently, we have shown that dichlorvos can induce microglial activation, and if not checked in time could ultimately induce neuronal apoptosis. However, this activation does not always pose a threat to the neurons. Activated microglia also secrete various neuronal growth factors, suggesting that they have beneficial roles in CNS repair. Therefore, it is essential to control their detrimental functions selectively. Here, we tried to find out how microglial cells behave when exposed to dichlorvos in either the presence or absence of potent nitric oxide scavenger and superoxide dismutase mimetic, 4-hydroxy TEMPO (4-HT). Wistar rat pups (1 day) were used to isolate and culture primary microglial cells. We found 4-HT pretreatment successfully attenuated the dichlorvos mediated microglial activation. Moreover, 4-HT pretreatment decreased the up-regulated levels of p53 and its downstream effector, p21. The expression of various cell cycle regulatorssuch as Chk2, CDC25a, and cyclin A remained close to their basal levelswhen 4-HT pretreatment was given. DNA fragmentation analysis showedsignificant reduction in the DNA damage of 4-HT pretreated microgliaas compared to dichlorvos treated cells. In addition to this, we found4-HT pretreatment prevented the microglial cells from undergoing apoptoticcell death even after 48 h of dichlorvos exposure. Taken together,our results showed 4-HT pretreatment could successfully amelioratethe dichlorvos induced microglial cell damage.