Adeno-associated virus vector-mediated expression of DJ-1 attenuates learning and memory deficits in 2, 2 ´, 4, 4´-tetrabromodiphenyl ether (BDE-47)-treated mice

Publication date: 5 April 2018 Source:Journal of Hazardous Materials, Volume 347 Author(s): Juan Zhuang, Shan Wang, Qun Shan, Zi-feng Zhang, Meng-qiu Li, Gui-hong Zheng, Shao-hua Fan, Dong-mei Wu, Bin Hu, Jun Lu, Yuan-lin Zheng Evidence indicates that oxidative stress is the central pathological feature of 2, 2´, 4, 4´-tetrabromodiphenyl ether (BDE-47)-induced neurotoxicity. Protein kinase C delta (PKCδ), an oxidative stress-sensitive kinase, can be proteolytically cleaved to yield a catalytically active fragment (PKCδ-CF) that is involved in various neurodegenerative disorders. Here, we showed that BDE-47 treatment increased ROS, malondialdehyde, and protein carbonyl levels in the mouse hippocampus. In turn, excessive ROS induced caspase-3-dependent PKCδ activation and stimulated NF-κB p65 nuclear translocation, resulting in inflammation in the mouse hippocampus. These changes caused learning and memory deficits in BDE-47-treated mice. Treatment with Z-DEVD-fmk, a caspase-3 inhibitor, or N-acetyl-L-cysteine, an antioxidant, blocked PKCδ activation and subsequently inhibited inflammation, thereby improving learning and memory deficits in BDE-47-treated mice. Our data further showed that activation of ROS-PKCδ signaling was associated with DJ-1 downregulation, which exerted neuroprotective effects against oxidative stress induced by different neurotoxic agents. Adeno-associated viral vector-mediated DJ-1 overexpression in the hippocampus effectively inhibi...
Source: Journal of Hazardous Materials - Category: Environmental Health Source Type: research