PMID- 29885849
OWN - NLM
STAT- MEDLINE
DCOM- 20190416
LR  - 20190416
IS  - 1872-7549 (Electronic)
IS  - 0166-4328 (Linking)
VI  - 356
DP  - 2019 Jan 1
TI  - PPARss/delta agonist alleviates NLRP3 inflammasome-mediated neuroinflammation in the 
      MPTP mouse model of Parkinson's disease.
PG  - 483-489
LID - S0166-4328(18)30215-8 [pii]
LID - 10.1016/j.bbr.2018.06.005 [doi]
AB  - Recent studies have indicated that peroxisome proliferator-activated receptor beta/delta 
      (PPARss/delta) agonists exert neuroprotective effects in the model of Parkinson's 
      disease (PD). Furthermore, PPARss/delta agonists have been shown to have potential 
      anti-inflammatory activity, but the underlying mechanisms remain obscure. 
      Emerging evidence indicates that the nucleotide-binding domain and 
      leucine-rich-repeat-protein 3 (NLRP3) inflammasome-mediated neuroinflammation 
      plays a crucial role in the pathogenesis of PD. In the present study we 
      investigate whether PPARss/delta agonists alleviate NLRP3-mediated neuroinflammation 
      in the 1- methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) mouse model of PD. 
      We administered GW501516, a selective and high-affinity PPARss/delta agonist, via 
      intracerebroventricular infusion. Locomotor activities were tested by open field 
      tests and the pole test. The levels of dopamine and its metabolites were 
      determined using highperformance liquid chromatography.Dopaminergic 
      neurodegeneration was assessed via Western blot analysis. The levels of oxidative 
      stress were detected via spectrophotometric assays. The expressions of 
      pro-inflammatory cytokines were measured by performing quantitative real-time 
      RT-PCR and ELISA. Western blot analysis was used to assess NLRP3 inflammasome 
      activation. Our results show that GW501516 reduced movement impairment in PD 
      mice; furthermore, it attenuated dopaminergic neurodegeneration in the midbrain 
      and the depletion of dopamine in the striatum and it inhibited inflammatory 
      reactions and NLRP3 inflammasome activation in the midbrain of PD mice. More 
      importantly, it attenuated astrocytic reaction but had no significant effect on 
      microglial reaction in the midbrain of PD mice. Collectively, our  fi ndings 
      demonstrate for the first time that the specific PPARss/delta agonist GW501516 
      alleviates NLRP3 inflammasome-mediated neuroinflammation in astrocytes in the 
      MPTP mouse model of PD.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Chen, Linfang
AU  - Chen L
AD  - Department of Neurology, The Affiliated Huaian No. 1 People's Hospital of Nanjing 
      Medical University, P.O. Box 223300, No. 6 Beijing Road West, Huaian, PR China.
FAU - Xue, Liujun
AU  - Xue L
AD  - Department of Neurology, The Affiliated Huaian No. 1 People's Hospital of Nanjing 
      Medical University, P.O. Box 223300, No. 6 Beijing Road West, Huaian, PR China.
FAU - Zheng, Jinlong
AU  - Zheng J
AD  - Department of Neurology, The Affiliated Huaian No. 1 People's Hospital of Nanjing 
      Medical University, P.O. Box 223300, No. 6 Beijing Road West, Huaian, PR China.
FAU - Tian, Xiangyang
AU  - Tian X
AD  - Department of Neurology, The Affiliated Huaian No. 1 People's Hospital of Nanjing 
      Medical University, P.O. Box 223300, No. 6 Beijing Road West, Huaian, PR China.
FAU - Zhang, Yingdong
AU  - Zhang Y
AD  - Department of Neurology, The Affiliated Nanjing Hospital of Nanjing Medical 
      University, P.O. Box 210006, No. 68 Changle Road, Nanjing, PR China. Electronic 
      address: zhangyingdong@aliyun.com.
FAU - Tong, Qiang
AU  - Tong Q
AD  - Department of Neurology, The Affiliated Huaian No. 1 People's Hospital of Nanjing 
      Medical University, P.O. Box 223300, No. 6 Beijing Road West, Huaian, PR China. 
      Electronic address: dr_tongqiang@126.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180608
PL  - Netherlands
TA  - Behav Brain Res
JT  - Behavioural brain research
JID - 8004872
RN  - 0 (Inflammasomes)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Nlrp3 protein, mouse)
RN  - 0 (PPAR-beta)
RN  - 9P21XSP91P (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine)
SB  - IM
MH  - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/pharmacology
MH  - Animals
MH  - Disease Models, Animal
MH  - Dopaminergic Neurons/drug effects
MH  - Inflammasomes/*drug effects
MH  - Inflammation/*metabolism
MH  - MPTP Poisoning/metabolism
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Microglia/drug effects
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/*drug effects
MH  - Neuroprotective Agents/*pharmacology
MH  - PPAR-beta/*agonists
MH  - Parkinson Disease/drug therapy/physiopathology
OTO - NOTNLM
OT  - Astrocytes
OT  - NLRP3
OT  - Neuroinflammation
OT  - PPARbeta/delta
OT  - Parkinson's disease
EDAT- 2018/06/11 06:00
MHDA- 2019/04/17 06:00
CRDT- 2018/06/11 06:00
PHST- 2018/02/07 00:00 [received]
PHST- 2018/06/06 00:00 [revised]
PHST- 2018/06/06 00:00 [accepted]
PHST- 2018/06/11 06:00 [pubmed]
PHST- 2019/04/17 06:00 [medline]
PHST- 2018/06/11 06:00 [entrez]
AID - S0166-4328(18)30215-8 [pii]
AID - 10.1016/j.bbr.2018.06.005 [doi]
PST - ppublish
SO  - Behav Brain Res. 2019 Jan 1;356:483-489. doi: 10.1016/j.bbr.2018.06.005. Epub 
      2018 Jun 8.