期刊
FOOD AND CHEMICAL TOXICOLOGY
卷 65, 期 -, 页码 280-292出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2013.12.046
关键词
Aroclor1254; Terpenoid-strengthened Ginkgo biloba; Ginsenoside Rg3; Antioxidant; BDNF/TrkB/DAT; NET
资金
- Ministry of Knowledge Economy (MKE)
- Korea Institute for Advancement of Technology (KIAT)
- Gangwon Leading Industry Office through the Leading Industry Development for Economic Region, Republic of Korea
- BK21 PLUS program
- National Research Foundation of Korea, Republic of Korea
Methylphenidate (MP) has become the primary drug of choice for treatment of attention-deficit/hyperactivity disorder (ADHD). However, its psychotropic effects severely hamper long-term clinical use. We evaluated the effects of YY162, which consists of terpenoid-strengthened Ginkgo biloba and ginsenoside Rg3, on the ADHD-like condition induced by Aroclor1254, because both components have been suggested to modulate oxidative stress, dopaminergic neurotransmission, and brain-derived neurotrophic factor (BDNF) signaling, which may be critical targets for understanding the pathogenesis of ADHD. YY162 attenuated the increase in reactive oxygen species (ROS) and decrease in BDNF levels induced by Aroclorl 254 in SH-SY5Y neuroblastoma cells. YY162 significantly attenuated Aroclorl 254-induced ADHD-like behavior and oxidative stress in ICR mice. Furthermore, YY162 attenuated reductions in p-TrkB, BDNF, dopamine transporter (DAT) and norepinephrine transporter (NET) expression. These attenuating effects of YY162 were comparable to those of MP. Importantly, K252a, a TrkB antagonist, counteracted the protective effects of YY162. Our results suggest that YY162 possesses significant protective activities against ADHD-like conditions with negligible behavioral side effects, and that interactive signaling between antioxidant potential and BDNF/TrkB receptor for the positive modulation of the DAT and NET is important for YY162-mediated neuroprotective activity. (C) 2014 Elsevier Ltd. All rights reserved.
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