Enhanced dopaminergic neurotoxicity mediated by MPTP in IL-32β transgenic mice

Yu Yeon Jung, Nikita Katila, Sabita Neupane, Sina Shadfar, Uttam Ojha, Sunil Bhurtel, Sunil Srivastav, Dong Ju Son, Pil-Hoon Park, Do Young Yoon, Jin Tae Hong, Dong-Young Choi

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)79-88
Number of pages10
JournalNeurochemistry International
Publication statusPublished - Jan 2017
Externally publishedYes


  • Parkinson's disease
  • Interleukin-32b
  • Microglia
  • 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP)
  • Neuroinflammation
  • Interleukin-32β
  • 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)


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