title: Naringin protects the nigrostriatal dopaminergic projection through induction of GDNF in a neurotoxin model of Parkinson's disease.
abstract: This study investigated the effect of naringin, a major flavonoid in grapefruit and citrus fruits, on the degeneration of the nigrostriatal dopaminergic (DA) projection in a neurotoxin model of Parkinson's disease (PD) in vivo and the potential underlying mechanisms focusing on the induction of glia-derived neurotrophic factor (GDNF), well known as an important neurotrophic factor involved in the survival of adult DA neurons. 1-Methyl-4-phenylpyridinium (MPP(+)) was unilaterally injected into the medial forebrain bundle of rat brains for a neurotoxin model of PD in the presence or absence of naringin by daily intraperitoneal injection. To ascertain whether naringin-induced GDNF contributes to neuroprotection, we further investigated the effects of intranigral injection of neutralizing antibodies against GDNF in the MPP(+) rat model of PD. Our observations demonstrate that naringin could increase the level of GDNF in DA neurons, contributing to neuroprotection in the MPP(+) rat model of PD, with activation of mammalian target of rapamycin complex 1. Moreover, naringin could attenuate the level of tumor necrosis factor-α in microglia increased by MPP(+)-induced neurotoxicity in the substantia nigra. These results indicate that naringin could impart to DA neurons the important ability to produce GDNF as a therapeutic agent against PD with anti-inflammatory effects, suggesting that naringin is a beneficial natural product for the prevention of DA degeneration in the adult brain.
authors.affiliation: School of Life Sciences and Biotechnology, Kyungpook National University, Daegu 702-701, Korea; KNU Creative BioResearch Group (BK21 Plus Program), Kyungpook National University, Daegu 702-701, Korea.
authors.forename: Eunju
authors.initials: E
authors.lastname: Leem
authors.affiliation: Neurodegeneration Control Research Center, School of Medicine, Kyung Hee University, Seoul 130-701, Korea.
authors.forename: Jin Han
authors.initials: JH
authors.lastname: Nam
authors.affiliation: School of Life Sciences and Biotechnology, Kyungpook National University, Daegu 702-701, Korea; KNU Creative BioResearch Group (BK21 Plus Program), Kyungpook National University, Daegu 702-701, Korea.
authors.forename: Min-Tae
authors.initials: MT
authors.lastname: Jeon
authors.affiliation: College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Korea; Korea Institute of Toxicology, Korea Research Institute of Chemical Technology, Yuseong, Daejeon 305-600, Korea.
authors.forename: Won-Ho
authors.initials: WH
authors.lastname: Shin
authors.affiliation: Department of Biochemistry and Signaling Disorder Research Center, Chungbuk National University, Cheongju 361-763, Korea.
authors.forename: So-Yoon
authors.initials: SY
authors.lastname: Won
authors.affiliation: College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Korea.
authors.forename: Sang-Joon
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Center for Food and Nutritional Genomics Research, Kyungpook National University, Daegu 702-701, Korea.
authors.forename: Myung-Sook
authors.initials: MS
authors.lastname: Choi
authors.affiliation: Neurodegeneration Control Research Center, School of Medicine, Kyung Hee University, Seoul 130-701, Korea.
authors.forename: Byung Kwan
authors.initials: BK
authors.lastname: Jin
authors.affiliation: Center for Food and Nutritional Genomics Research, Kyungpook National University, Daegu 702-701, Korea.
authors.forename: Un Ju
authors.initials: UJ
authors.lastname: Jung
authors.affiliation: School of Life Sciences and Biotechnology, Kyungpook National University, Daegu 702-701, Korea; KNU Creative BioResearch Group (BK21 Plus Program), Kyungpook National University, Daegu 702-701, Korea; Institute of Life Science and Biotechnology, Kyungpook National University, Daegu 702-701, Korea; Brain Science and Engineering Institute, Kyungpook National University, Daegu 700-842, Korea. Electronic address: srk75@knu.ac.kr.
authors.forename: Sang Ryong
authors.initials: SR
authors.lastname: Kim
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D000818:Animals; D004195:Disease Models, Animal; D004298:Dopamine / Q000502:physiology*; D005260:Female; D044950:Flavanones / Q000494:pharmacology*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000276:immunology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010300:Parkinson Disease / Q000503:physiopathology*; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects*
chemical_list: D044950:Flavanones; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; C005274:naringin; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine
keywords: 1-Methyl-4-phenylpyridinium; GDNF; Naringin; Neuroprotection; Parkinson's disease