• KSBNS 2024


Original Article

Exp Neurobiol 2018; 27(4): 309-319

Published online August 30, 2018

© The Korean Society for Brain and Neural Sciences

Interleukin-4 Contributes to Degeneration of Dopamine Neurons in the Lipopolysaccharide-treated Substantia Nigra in vivo

Eugene Bok1, Eun Ju Cho2, Eun Sook Chung2, Won-Ho Shin1*, and Byung Kwan Jin2*

1Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon 34114, Korea.

2Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Korea.

Correspondence to: *To whom correspondence should be addressed.
Won-Ho Shin, TEL: 82-42-610-8088, FAX: 82-42-610-8157
Byung Kwan Jin, TEL: 82-2-969-4563, FAX: 82-2-969-4570

Received: July 4, 2018; Revised: July 24, 2018; Accepted: August 3, 2018

The present study investigated the effects of interleukin (IL)-4 on dopamine (DA) neurons in the substantia nigra (SN) in vivo of lipopolysaccharide (LPS)-treated rat. Tyrosine hydroxylase immunohistochemistry showed a significant loss of nigral DA neurons at 3 and 7 day post-LPS. In parallel, IL-4 immunoreactivity was upregulated as early as 1 day, reached a peak at 3 day and remained elevated at 7 day post-LPS. IL-4 immunoreactivity was detected exclusively in microglia. IL-4 neutralizing antibody (NA) significantly increased survival of DA neurons in LPS-treated SN in vivo by inhibiting microglial activation and production of proinflammatory mediator such as IL-1β as assessed by immunihistochemical, RT-PCR and ELISA analysis, respectively. Accompanying neuroprotection are IL-4NA effects on decreased disruption of blood-brain barrier and astrocytes. The present data suggest that endogenously expressed IL-4 from reactive microglia may be involved in the neuropathological processes of degeneration of DA neurons occurring in Parkinson's disease.

Graphical Abstract

Keywords: Interleukin-4, Parkinson disease, Substantia nigra, Dopaminergic neurons, Lipopolysaccharides