Enhanced dopaminergic neurotoxicity mediated by MPTP in IL-32β transgenic mice. (January 2017)

• Record Type: Journal Article
• Authors: Jung, Yu Yeon; Katila, Nikita; Neupane, Sabita; Shadfar, Sina; Ojha, Uttam; Bhurtel, Sunil; Srivastav, Sunil; Son, Dong Ju; Park, Pil-Hoon; Yoon, Do Young; Hong, Jin Tae; Choi, Dong-Young
• Is Part Of: Neurochemistry international. Volume 102(2016)
• Page Start: 79
• Page End: 88
• Publication Date: 2017-01
• Subjects: Parkinson's disease -- Interleukin-32β -- Microglia -- 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) -- Neuroinflammation; PD Parkinson's disease -- iNOS Inducible nitric oxide synthase -- COX Cyclooxygenase -- IL Interleukin -- TNF Tumor necrosis factor -- MPTP 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine -- STAT3 Signal transducer and activator of transcription 3 -- Tg Transgenic -- nTg Non-transgenic -- ORP Over all rod performance -- DOPAC 3, 4-dihydroxyphenylacetic acid -- HVA Homovanilic acid -- TH Tyrosine hydroxylase -- IBA1 Ionized calcium-binding adapter molecule 1 -- GFAP Glial fibrillary acidic protein -- NOX NADPH oxidase -- DAPK Death-associated protein kinase -- JNK Jun amino-terminal kinases -- MAPK Mitogen-activated protein kinase -- ERK 1/2 Extracellular signal regulated kinases 1 and 2; Neurochemistry -- Periodicals; Neurochemistry -- Periodicals; Neurochimie -- Périodiques; Neurochemistry; Periodicals; 612.804205
• DOI: 10.1016/j.neuint.2016.12.002
• Languages: English
• ISSNs: 0197-0186

Abstract

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. Highlights: Effects of IL-32β on MPTP neurotoxicity were tested. Transgenic IL-32β exaggerated the dopaminergic neurotoxicity. Enhanced neuroinflammation may be related to increased toxicity.