Gemfibrozil Protects Dopaminergic Neurons in a Mouse Model of Parkinson's Disease via PPARα-Dependent Astrocytic GDNF Pathway.
Animals
Astrocytes
/ drug effects
Brain
/ drug effects
Cytochrome P-450 CYP2C8 Inhibitors
/ pharmacology
Dopaminergic Neurons
/ drug effects
Gemfibrozil
/ pharmacology
Glial Cell Line-Derived Neurotrophic Factor
/ metabolism
Mice
Mice, Inbred C57BL
Neuroprotective Agents
/ pharmacology
PPAR alpha
/ metabolism
Parkinsonian Disorders
/ metabolism
Signal Transduction
/ drug effects
GDNF
PPARα
gemfibrozil
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
ISSN: 1529-2401
Titre abrégé: J Neurosci
Pays: United States
ID NLM: 8102140
Informations de publication
Date de publication:
10 03 2021
10 03 2021
Historique:
received:
19
12
2019
revised:
16
01
2021
accepted:
18
01
2021
pubmed:
31
1
2021
medline:
12
6
2021
entrez:
30
1
2021
Statut:
ppublish
Résumé
Parkinson's disease (PD) is the most common neurodegenerative movement disorder in humans. Despite intense investigations, effective therapies are not yet available to halt the progression of PD. Gemfibrozil, a Food and Drug Administration-approved lipid-lowering drug, is known to decrease the risk of coronary heart disease by increasing the level of high-density lipoprotein cholesterol and decreasing the level of low-density lipoprotein cholesterol. This study underlines the importance of gemfibrozil in protecting dopaminergic neurons in an animal model of PD. Oral administration of the human equivalent dose of gemfibrozil protected tyrosine hydroxylase (TH)-positive dopaminergic neurons in the substantia nigra pars compacta and TH fibers in the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-insulted mice of both sexes. Accordingly, gemfibrozil also normalized striatal neurotransmitters and improved locomotor activities in MPTP-intoxicated mice. Gemfibrozil-mediated protection of the nigrostriatal and locomotor activities in WT but not PPARα
Identifiants
pubmed: 33514677
pii: JNEUROSCI.3018-19.2021
doi: 10.1523/JNEUROSCI.3018-19.2021
pmc: PMC8018777
doi:
Substances chimiques
Cytochrome P-450 CYP2C8 Inhibitors
0
Glial Cell Line-Derived Neurotrophic Factor
0
Neuroprotective Agents
0
PPAR alpha
0
Gemfibrozil
Q8X02027X3
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
2287-2300Subventions
Organisme : BLRD VA
ID : I01 BX003033
Pays : United States
Organisme : BLRD VA
ID : IK6 BX004982
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS083054
Pays : United States
Organisme : NINDS NIH HHS
ID : R21 NS108025
Pays : United States
Informations de copyright
Copyright © 2021 the authors.
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