DF3016A induces increased BDNF transcription in ischemic neuroinflammation injury.
Animals
Apoptosis
/ drug effects
Brain Ischemia
/ genetics
Brain-Derived Neurotrophic Factor
/ genetics
Complement Inactivating Agents
/ pharmacology
Methyl-CpG-Binding Protein 2
/ genetics
Neurons
/ drug effects
Rats
Rats, Sprague-Dawley
Receptor, Anaphylatoxin C5a
/ antagonists & inhibitors
Signal Transduction
/ drug effects
Transcription, Genetic
/ drug effects
BDNF
C5aR
Complement
Neuroinflammation
OGD/R
microRNA-132
Journal
Brain research
ISSN: 1872-6240
Titre abrégé: Brain Res
Pays: Netherlands
ID NLM: 0045503
Informations de publication
Date de publication:
01 12 2020
01 12 2020
Historique:
received:
27
05
2020
revised:
27
07
2020
accepted:
11
08
2020
pubmed:
9
9
2020
medline:
27
10
2021
entrez:
8
9
2020
Statut:
ppublish
Résumé
C5a is a crucial terminal effector of the C cascade, mostly involved in pain and neuroinflammatory conditions. DF3016A is a novel potent and selective C5a receptor (C5aR) inhibitor that crosses the blood-brain barrier (BBB) and may have pharmacological properties. We have previously demonstrated a protective effect of DF3016A on injured primary cortical neurons by oxygen-glucose deprivation-reoxygenation (OGD/R) model to mimic the neuroinflammatory process. Here, we investigated the molecular pathway and factors involved in the neuroprotection previously reported. Our findings show that DF3016A protects against the neuroinflammatory insult by activating brain-derived neurotrophic factor (BDNF) transcription pathway, which involves methyl CpG-binding protein 2 (MeCP2) and microRNA-132 (miR-132) regulatory factors, both required in nociceptive signaling and neuroinflammation. Further in vivo investigations will confirm the functionality of the DF3016A molecule as a therapeutic resource in neuroinflammation and pain injuries.
Identifiants
pubmed: 32898508
pii: S0006-8993(20)30415-7
doi: 10.1016/j.brainres.2020.147057
pii:
doi:
Substances chimiques
Brain-Derived Neurotrophic Factor
0
Complement Inactivating Agents
0
Methyl-CpG-Binding Protein 2
0
Receptor, Anaphylatoxin C5a
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
147057Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.