title: Enhanced dopaminergic neurotoxicity mediated by MPTP in IL-32β transgenic mice.
abstract: Parkinson's disease (PD) is a neurodegenerative disorder characterized by prominent loss of the nigral dopaminergic neurons and motor symptoms, such as resting tremor and bradykinesia. Evidence suggests that neuroinflammation may play a critical role in PD pathogenesis. Interleukin (IL)-32 is a newly-identified proinflammatory cytokine, which regulates innate and adaptive immune responses by activating p38 MAPK and NF-κB signaling pathways. The cytokine has been implicated in cancers and autoimmune, inflammatory, and infectious diseases. In this study, we attempted to identify the effects of IL-32β on dopaminergic neurotoxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), using IL-32β transgenic mice. Male wild type and IL-32β transgenic mice received intraperitoneal injections of vehicle or MPTP (15 mg/kg × 4). Immunohistochemistry showed that overexpression of IL-32β significantly increased MPTP-mediated loss of dopaminergic neurons in the substantia nigra and deletion of tyrosine hydroxylase-positive fibers in the striatum. Dopamine depletion in the striatum and deficit in locomotor activity were enhanced in IL-32β transgenic mice. These results were accompanied by higher neuroinflammatory responses in the brains of transgenic mice. Finally, we found that IL-32β exaggerated MPTP-mediated activation of p38 MAPK and JNK pathways, which have been shown to be involved in MPTP neurotoxicity. These results suggest that IL-32β exacerbates MPTP neurotoxicity through enhanced neuroinflammatory responses.
authors.affiliation: Department of Dental Hygiene, Gwang Yang Health College, Gwangyang 57764, Republic of Korea. Electronic address: hygienkh@naver.com.
authors.forename: Yu Yeon
authors.initials: YY
authors.lastname: Jung
authors.affiliation: College of Pharmacy, Yeungnam University, 280 Daehak-ro, Gyeongsan, Gyeongbuk 38541, Republic of Korea. Electronic address: nikitakatila28@gmail.com.
authors.forename: Nikita
authors.initials: N
authors.lastname: Katila
authors.affiliation: College of Pharmacy, Yeungnam University, 280 Daehak-ro, Gyeongsan, Gyeongbuk 38541, Republic of Korea. Electronic address: sabita_neupane@hotmail.com.
authors.forename: Sabita
authors.initials: S
authors.lastname: Neupane
authors.affiliation: College of Pharmacy, Yeungnam University, 280 Daehak-ro, Gyeongsan, Gyeongbuk 38541, Republic of Korea. Electronic address: sina.shadfar@yahoo.com.
authors.forename: Sina
authors.initials: S
authors.lastname: Shadfar
authors.affiliation: College of Pharmacy, Yeungnam University, 280 Daehak-ro, Gyeongsan, Gyeongbuk 38541, Republic of Korea. Electronic address: uttamojha47@gmail.com.
authors.forename: Uttam
authors.initials: U
authors.lastname: Ojha
authors.affiliation: College of Pharmacy, Yeungnam University, 280 Daehak-ro, Gyeongsan, Gyeongbuk 38541, Republic of Korea. Electronic address: bhurtelsunil11@gmail.com.
authors.forename: Sunil
authors.initials: S
authors.lastname: Bhurtel
authors.affiliation: College of Pharmacy, Yeungnam University, 280 Daehak-ro, Gyeongsan, Gyeongbuk 38541, Republic of Korea. Electronic address: sunsri2003@hotmail.com.
authors.forename: Sunil
authors.initials: S
authors.lastname: Srivastav
authors.affiliation: College of Pharmacy, Chungbuk National University, 12 Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk 28644, Republic of Korea. Electronic address: sondj1@chungbuk.ac.kr.
authors.forename: Dong Ju
authors.initials: DJ
authors.lastname: Son
authors.affiliation: College of Pharmacy, Yeungnam University, 280 Daehak-ro, Gyeongsan, Gyeongbuk 38541, Republic of Korea. Electronic address: parkp@yu.ac.kr.
authors.forename: Pil-Hoon
authors.initials: PH
authors.lastname: Park
authors.affiliation: Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea. Electronic address: ydy4218@konkuk.ac.kr.
authors.forename: Do Young
authors.initials: DY
authors.lastname: Yoon
authors.affiliation: College of Pharmacy, Chungbuk National University, 12 Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk 28644, Republic of Korea. Electronic address: jinthong@chungbuk.ac.kr.
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
authors.affiliation: College of Pharmacy, Yeungnam University, 280 Daehak-ro, Gyeongsan, Gyeongbuk 38541, Republic of Korea. Electronic address: dychoi@yu.ac.kr.
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Choi
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000187:drug effects*; D007378:Interleukins / Q000235:genetics*; D020267:MPTP Poisoning / Q000378:metabolism; D008822:Mice, Transgenic; D013378:Substantia Nigra / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D007378:Interleukins; C569037:interleukin-32, mouse; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine
keywords: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP); Interleukin-32β; Microglia; Neuroinflammation; Parkinson's disease