Unknown

Dataset Information

0

Microglia-Derived Cytokines/Chemokines Are Involved in the Enhancement of LPS-Induced Loss of Nigrostriatal Dopaminergic Neurons in DJ-1 Knockout Mice.


ABSTRACT: Mutation of DJ-1 (PARK7) has been linked to the development of early-onset Parkinson's disease (PD). However, the underlying molecular mechanism is still unclear. This study is aimed to compare the sensitivity of nigrostriatal dopaminergic neurons to lipopolysaccharide (LPS) challenge between DJ-1 knockout (KO) and wild-type (WT) mice, and explore the underlying cellular and molecular mechanisms. Our results found that the basal levels of interferon (IFN)-? (the hub cytokine) and interferon-inducible T-cell alpha chemoattractant (I-TAC) (a downstream mediator) were elevated in the substantia nigra of DJ-1 KO mice and in microglia cells with DJ-1 deficiency, and the release of cytokine/chemokine was greatly enhanced following LPS administration in the DJ-1 deficient conditions. In addition, direct intranigral LPS challenge caused a greater loss of nigrostriatal dopaminergic neurons and striatal dopamine content in DJ-1 KO mice than in WT mice. Furthermore, the sensitization of microglia cells to LPS challenge to release IFN-? and I-TAC was via the enhancement of NF-?B signaling, which was antagonized by NF-?B inhibitors. LPS-induced increase in neuronal death in the neuron-glia co-culture was enhanced by DJ-1 deficiency in microglia, which was antagonized by the neutralizing antibodies against IFN-? or I-TAC. These results indicate that DJ-1 deficiency sensitizes microglia cells to release IFN-? and I-TAC and causes inflammatory damage to dopaminergic neurons. The interaction between the genetic defect (i.e. DJ-1) and inflammatory factors (e.g. LPS) may contribute to the development of PD.

SUBMITTER: Chien CH 

PROVIDER: S-EPMC4794203 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

altmetric image

Publications

Microglia-Derived Cytokines/Chemokines Are Involved in the Enhancement of LPS-Induced Loss of Nigrostriatal Dopaminergic Neurons in DJ-1 Knockout Mice.

Chien Chia-Hung CH   Lee Ming-Jen MJ   Liou Houng-Chi HC   Liou Horng-Huei HH   Fu Wen-Mei WM  

PloS one 20160316 3


Mutation of DJ-1 (PARK7) has been linked to the development of early-onset Parkinson's disease (PD). However, the underlying molecular mechanism is still unclear. This study is aimed to compare the sensitivity of nigrostriatal dopaminergic neurons to lipopolysaccharide (LPS) challenge between DJ-1 knockout (KO) and wild-type (WT) mice, and explore the underlying cellular and molecular mechanisms. Our results found that the basal levels of interferon (IFN)-γ (the hub cytokine) and interferon-indu  ...[more]

Similar Datasets

| S-EPMC4831782 | biostudies-literature
| S-EPMC6623418 | biostudies-literature
| S-EPMC6642214 | biostudies-literature
| S-EPMC8562009 | biostudies-literature
| S-EPMC4465557 | biostudies-literature
| S-EPMC5552514 | biostudies-other
2015-01-01 | GSE63246 | GEO
2015-01-01 | E-GEOD-63246 | biostudies-arrayexpress
| S-EPMC5116056 | biostudies-literature
| S-EPMC6741442 | biostudies-literature