title: 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.affiliation: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea.
authors.forename: Yunsung
authors.initials: Y
authors.lastname: Nam
authors.affiliation: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea.
authors.forename: Eun-Joo
authors.initials: EJ
authors.lastname: Shin
authors.affiliation: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea.
authors.forename: Seung Woo
authors.initials: SW
authors.lastname: Shin
authors.affiliation: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea.
authors.forename: Yong Kwang
authors.initials: YK
authors.lastname: Lim
authors.affiliation: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea.
authors.forename: Jong Ho
authors.initials: JH
authors.lastname: Jung
authors.affiliation: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea.
authors.forename: Jeong Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Research Center, Yuyu Pharma Inc., GyeongGi Bio-Center 864-1, Suwon 443-766, Republic of Korea.
authors.forename: Jong Ryul
authors.initials: JR
authors.lastname: Ha
authors.affiliation: Research Center, Yuyu Pharma Inc., GyeongGi Bio-Center 864-1, Suwon 443-766, Republic of Korea.
authors.forename: Jong Seok
authors.initials: JS
authors.lastname: Chae
authors.affiliation: Department of Oriental Medical Food & Nutrition, Semyung University, Jecheon 390-711, Republic of Korea.
authors.forename: Sung Kwon
authors.initials: SK
authors.lastname: Ko
authors.affiliation: Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Choon-Gon
authors.initials: CG
authors.lastname: Jang
authors.affiliation: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea. Electronic address: kimhc@kangwon.ac.kr.
authors.forename: Hyoung-Chun
authors.initials: HC
authors.lastname: Kim
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000503:physiopathology; D001522:Behavior, Animal; D045744:Cell Line, Tumor; D020111:Chlorodiphenyl (54% Chlorine) / Q000633:toxicity*; D004195:Disease Models, Animal; D004338:Drug Combinations; D005260:Female; D036145:Ginsenosides / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010936:Plant Extracts / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D004338:Drug Combinations; D036145:Ginsenosides; D010936:Plant Extracts; C000592553:YY162; D020111:Chlorodiphenyl (54% Chlorine)
keywords: Antioxidant; Aroclor1254; BDNF/TrkB/DAT; Ginsenoside Rg3; NET; Terpenoid-strengthened Ginkgo biloba