Exp Neurobiol.  2018 Aug;27(4):309-319. 10.5607/en.2018.27.4.309.

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

Affiliations
  • 1Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon 34114, Korea. whshin@kitox.re.kr
  • 2Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Korea. bkjin@khu.ac.kr

Abstract

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.

Keyword

Interleukin-4; Parkinson disease; Substantia nigra; Dopaminergic neurons; Lipopolysaccharides

MeSH Terms

Animals
Antibodies, Neutralizing
Astrocytes
Blood-Brain Barrier
Dopamine*
Dopaminergic Neurons*
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
Interleukin-4*
Interleukins
Lipopolysaccharides
Microglia
Neurons
Neuroprotection
Parkinson Disease
Rats
Substantia Nigra*
Tyrosine 3-Monooxygenase
Antibodies, Neutralizing
Dopamine
Interleukin-4
Interleukins
Lipopolysaccharides
Tyrosine 3-Monooxygenase
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