PMID- 32484574
OWN - NLM
STAT- MEDLINE
DCOM- 20210513
LR  - 20210513
IS  - 1873-3468 (Electronic)
IS  - 0014-5793 (Linking)
VI  - 594
IP  - 17
DP  - 2020 Sep
TI  - Knockdown of microglial Cav2.2 N-type voltage-dependent Ca(2+) channel 
      ameliorates behavioral deficits in a mouse model of Parkinson's disease.
PG  - 2914-2922
LID - 10.1002/1873-3468.13853 [doi]
AB  - Cav2.2 N-type voltage-dependent Ca(2+) channel (VDCC) expressed in neurons is 
      known to be essential for neurotransmitter release. We have shown previously that 
      this channel is also expressed in nonexcitable microglia and plays pivotal roles 
      in microglial functions. Here, we have examined the effects of microglia-specific 
      knockdown (KD) of Cav2.2 channel in a mouse model of Parkinson's disease (PD). We 
      found that the KD of Cav2.2 channel reduces the accumulation of microglia in the 
      substantia nigra and ameliorates the behavioral deficits in PD model mice. These 
      results are in marked contrast with those found in microglia-specific KD of 
      Cav1.2 L-type channel, where exacerbated symptoms are observed. Our results 
      suggest that blockade of microglial Cav2.2 N-type VDCC is beneficial for the 
      treatment of PD.
CI  - (c) 2020 Federation of European Biochemical Societies.
FAU - Saegusa, Hironao
AU  - Saegusa H
AUID- ORCID: 0000-0002-9757-0055
AD  - Department of Pharmacology and Neurobiology, Graduate School of Medicine, Tokyo 
      Medical and Dental University (TMDU), Tokyo, Japan.
FAU - Li, Xu
AU  - Li X
AD  - Department of Pharmacology and Neurobiology, Graduate School of Medicine, Tokyo 
      Medical and Dental University (TMDU), Tokyo, Japan.
FAU - Wang, Xinshuang
AU  - Wang X
AD  - Department of Pharmacology and Neurobiology, Graduate School of Medicine, Tokyo 
      Medical and Dental University (TMDU), Tokyo, Japan.
FAU - Kayakiri, Midori
AU  - Kayakiri M
AD  - Department of Pharmacology and Neurobiology, Graduate School of Medicine, Tokyo 
      Medical and Dental University (TMDU), Tokyo, Japan.
FAU - Tanabe, Tsutomu
AU  - Tanabe T
AUID- ORCID: 0000-0003-3000-9105
AD  - Department of Pharmacology and Neurobiology, Graduate School of Medicine, Tokyo 
      Medical and Dental University (TMDU), Tokyo, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200616
PL  - England
TA  - FEBS Lett
JT  - FEBS letters
JID - 0155157
RN  - 0 (CACNA1C protein, mouse)
RN  - 0 (Cacna1b protein, mouse)
RN  - 0 (Calcium Channels, L-Type)
RN  - 0 (Calcium Channels, N-Type)
RN  - 0 (Selective Estrogen Receptor Modulators)
RN  - 094ZI81Y45 (Tamoxifen)
RN  - 9P21XSP91P (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine)
SB  - IM
MH  - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/administration & dosage
MH  - Animals
MH  - Calcium Channels, L-Type/deficiency/genetics
MH  - Calcium Channels, N-Type/deficiency/*genetics
MH  - Cell Count
MH  - Cell Death/genetics
MH  - Dopaminergic Neurons/*metabolism/pathology
MH  - Gene Expression
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microglia/*metabolism/pathology
MH  - Parkinsonian Disorders/chemically induced/*genetics/metabolism/pathology
MH  - Psychomotor Performance/physiology
MH  - Selective Estrogen Receptor Modulators/pharmacology
MH  - Substantia Nigra/*metabolism/pathology
MH  - Tamoxifen/pharmacology
OTO - NOTNLM
OT  - Cav2.2
OT  - MPTP
OT  - N-type voltage-dependent Ca2+ channel
OT  - Parkinson's disease
OT  - VDCC
OT  - microglia
EDAT- 2020/06/03 06:00
MHDA- 2021/05/14 06:00
CRDT- 2020/06/03 06:00
PHST- 2020/02/17 00:00 [received]
PHST- 2020/05/13 00:00 [revised]
PHST- 2020/05/20 00:00 [accepted]
PHST- 2020/06/03 06:00 [pubmed]
PHST- 2021/05/14 06:00 [medline]
PHST- 2020/06/03 06:00 [entrez]
AID - 10.1002/1873-3468.13853 [doi]
PST - ppublish
SO  - FEBS Lett. 2020 Sep;594(17):2914-2922. doi: 10.1002/1873-3468.13853. Epub 2020 
      Jun 16.