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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2018

Open Access 01-12-2018 | Research

The small molecule CA140 inhibits the neuroinflammatory response in wild-type mice and a mouse model of AD

Authors: Ju-Young Lee, Jin Han Nam, Youngpyo Nam, Hye Yeon Nam, Gwangho Yoon, Eunhwa Ko, Sang-Bum Kim, Mahealani R Bautista, Christina C Capule, Takaoki Koyanagi, Geoffray Leriche, Hwan Geun Choi, Jerry Yang, Jeongyeon Kim, Hyang-Sook Hoe

Published in: Journal of Neuroinflammation | Issue 1/2018

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Abstract

Background

Neuroinflammation is associated with neurodegenerative diseases, including Alzheimer’s disease (AD). Thus, modulating the neuroinflammatory response represents a potential therapeutic strategy for treating neurodegenerative diseases. Several recent studies have shown that dopamine (DA) and its receptors are expressed in immune cells and are involved in the neuroinflammatory response. Thus, we recently developed and synthesized a non-self-polymerizing analog of DA (CA140) and examined the effect of CA140 on neuroinflammation.

Methods

To determine the effects of CA140 on the neuroinflammatory response, BV2 microglial cells were pretreated with lipopolysaccharide (LPS, 1 μg/mL), followed by treatment with CA140 (10 μM) and analysis by reverse transcription-polymerase chain reaction (RT-PCR). To examine whether CA140 alters the neuroinflammatory response in vivo, wild-type mice were injected with both LPS (10 mg/kg, intraperitoneally (i.p.)) and CA140 (30 mg/kg, i.p.), and immunohistochemistry was performed. In addition, familial AD (5xFAD) mice were injected with CA140 or vehicle daily for 2 weeks and examined for microglial and astrocyte activation.

Results

Pre- or post-treatment with CA140 differentially regulated proinflammatory responses in LPS-stimulated microglia and astrocytes. Interestingly, CA140 regulated D1R levels to alter LPS-induced proinflammatory responses. CA140 significantly downregulated LPS-induced phosphorylation of ERK and STAT3 in BV2 microglia cells. In addition, CA140-injected wild-type mice exhibited significantly decreased LPS-induced microglial and astrocyte activation. Moreover, CA140-injected 5xFAD mice exhibited significantly reduced microglial and astrocyte activation.

Conclusions

CA140 may be beneficial for preventing and treating neuroinflammatory-related diseases, including AD.
Appendix
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Metadata
Title
The small molecule CA140 inhibits the neuroinflammatory response in wild-type mice and a mouse model of AD
Authors
Ju-Young Lee
Jin Han Nam
Youngpyo Nam
Hye Yeon Nam
Gwangho Yoon
Eunhwa Ko
Sang-Bum Kim
Mahealani R Bautista
Christina C Capule
Takaoki Koyanagi
Geoffray Leriche
Hwan Geun Choi
Jerry Yang
Jeongyeon Kim
Hyang-Sook Hoe
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2018
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-018-1321-3

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