PMID- 37382264
OWN - NLM
STAT- MEDLINE
DCOM- 20230630
LR  - 20240219
IS  - 2050-4527 (Electronic)
IS  - 2050-4527 (Linking)
VI  - 11
IP  - 6
DP  - 2023 Jun
TI  - Melatonin regulates microglial polarization to M2 cell via RhoA/ROCK signaling 
      pathway in epilepsy.
PG  - e900
LID - 10.1002/iid3.900 [doi]
LID - e900
AB  - BACKGROUND: Melatonin (MEL), an endogenous hormone, has been widely investigated 
      in neurological diseases. Microglia (MG), a resident immunocyte localizing in 
      central nervous system is reported to play important functions in the animal 
      model of temporal lobe epilepsy (TLE). Some evidence showed that MEL influenced 
      activation of MG, but the detailed model of action that MEL plays in remains 
      uncertain. METHODS: In this study, we established a model of TLE in mice by 
      stereotactic injection of kainic acid (KA). We treated the mice with MEL. 
      Lipopolysaccharide, ROCK2-knockdown (ROCK-KD) and -overexpression (ROCK-OE) of 
      lentivirus-treated cells were used in cell experiments to simulate an in vitro 
      inflammatory model. RESULTS: The results of electrophysiological tests showed 
      that MEL reduced frequency and severity of seizure. The results of behavioral 
      tests indicated MEL improved cognition, learning, and memory ability. 
      Histological evidences demonstrated a significant reduction of neuronal death in 
      the hippocampus. In vivo study showed that MEL changed the polarization status of 
      MG from a proinflammatory M1 phenotype to an anti-inflammatory M2 phenotype by 
      inversely regulating the RhoA/ROCK signaling pathway. In cytological study, we 
      found that MEL had a significant protective effect in LPS-treated BV-2 cells and 
      ROCK-KD cells, while the protective effect of MEL was significantly attenuated in 
      ROCK-OE cells. CONCLUSION: MEL played an antiepileptic role in the KA-induced TLE 
      modeling mice both in behavioral and histological levels, and changed MG 
      polarization status by regulating the RhoA/ROCK signaling pathway.
CI  - (c) 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & 
      Sons Ltd.
FAU - Li, Pingping
AU  - Li P
AD  - Department of Neurosurgery, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
FAU - Ji, Xuefei
AU  - Ji X
AD  - Department of Neurosurgery, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
FAU - Shan, Ming
AU  - Shan M
AD  - Department of Neurosurgery, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
FAU - Wang, Yi
AU  - Wang Y
AD  - Department of Neurosurgery, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
FAU - Dai, Xingliang
AU  - Dai X
AD  - Department of Neurosurgery, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
FAU - Yin, Mengyuan
AU  - Yin M
AD  - Department of Neurosurgery, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
FAU - Liu, Yunlong
AU  - Liu Y
AD  - First Clinical Medical College, Anhui Medical University, Hefei, China.
FAU - Guan, Liao
AU  - Guan L
AD  - Department of Neurosurgery, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
FAU - Ye, Lei
AU  - Ye L
AUID- ORCID: 0000-0002-5079-8730
AD  - Department of Neurosurgery, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
FAU - Cheng, Hongwei
AU  - Cheng H
AD  - Department of Neurosurgery, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Immun Inflamm Dis
JT  - Immunity, inflammation and disease
JID - 101635460
RN  - JL5DK93RCL (Melatonin)
RN  - 0 (Lipopolysaccharides)
SB  - IM
MH  - Animals
MH  - Mice
MH  - *Melatonin/pharmacology
MH  - Microglia
MH  - *Epilepsy
MH  - Signal Transduction
MH  - Lipopolysaccharides/toxicity
PMC - PMC10266134
OTO - NOTNLM
OT  - RhoA/ROCK
OT  - epilepsy
OT  - melatonin
OT  - microglia
OT  - polarization
COIS- The authors declare no conflict of interest.
EDAT- 2023/06/29 13:42
MHDA- 2023/06/30 06:42
PMCR- 2023/06/14
CRDT- 2023/06/29 07:14
PHST- 2023/04/26 00:00 [revised]
PHST- 2023/01/27 00:00 [received]
PHST- 2023/05/17 00:00 [accepted]
PHST- 2023/06/30 06:42 [medline]
PHST- 2023/06/29 13:42 [pubmed]
PHST- 2023/06/29 07:14 [entrez]
PHST- 2023/06/14 00:00 [pmc-release]
AID - IID3900 [pii]
AID - 10.1002/iid3.900 [doi]
PST - ppublish
SO  - Immun Inflamm Dis. 2023 Jun;11(6):e900. doi: 10.1002/iid3.900.