YY162 prevents ADHD-like behavioral side effects and cytotoxicity induced by Aroclor1254 via interactive signaling between antioxidant potential, BDNF/TrkB, DAT and NET.

Abstract

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 Aroclor1254 in SH-SY5Y neuroblastoma cells. YY162 significantly attenuated Aroclor1254-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.

• Authors: Yunsung Nam, Eun-Joo Shin, Seung Woo Shin, Yong Kwang Lim, Jong Ho Jung, Jeong Hyun Lee, Jong Ryul Ha, Jong Seok Chae, Sung Kwon Ko, Ji Hoon Jeong, Choon-Gon Jang, Hyoung-Chun Kim
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 65 Pg. 280-92 (Mar 2014) ISSN: 1873-6351 [Electronic] England
• PMID: 24394491 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Antioxidants
• Drug Combinations
• Ginsenosides
• Plant Extracts
• YY162
• Chlorodiphenyl (54% Chlorine)

Topics

• Animals
• Antioxidants (metabolism)
• Attention Deficit Disorder with Hyperactivity (drug therapy, physiopathology)
• Behavior, Animal
• Cell Line, Tumor
• Chlorodiphenyl (54% Chlorine) (toxicity)
• Disease Models, Animal
• Drug Combinations
• Female
• Ginsenosides (therapeutic use)
• Humans
• Male
• Mice
• Mice, Inbred ICR
• Plant Extracts (therapeutic use)
• Signal Transduction (drug effects)