PMID- 35145238
OWN - NLM
STAT- MEDLINE
DCOM- 20221004
LR  - 20231002
IS  - 1745-7254 (Electronic)
IS  - 1671-4083 (Print)
IS  - 1671-4083 (Linking)
VI  - 43
IP  - 10
DP  - 2022 Oct
TI  - Connexin 43: insights into candidate pathological mechanisms of depression and 
      its implications in antidepressant therapy.
PG  - 2448-2461
LID - 10.1038/s41401-022-00861-2 [doi]
AB  - Major depressive disorder (MDD), a chronic and recurrent disease characterized by 
      anhedonia, pessimism or even suicidal thought, remains a major chronic mental 
      concern worldwide. Connexin 43 (Cx43) is the most abundant connexin expressed in 
      astrocytes and forms the gap junction channels (GJCs) between astrocytes, the 
      most abundant and functional glial cells in the brain. Astrocytes regulate 
      neurons' synaptic strength and function by expressing receptors and regulating 
      various neurotransmitters. Astrocyte dysfunction causes synaptic abnormalities, 
      which are related to various mood disorders, e.g., depression. Increasing 
      evidence suggests a crucial role of Cx43 in the pathogenesis of depression. 
      Depression down-regulates Cx43 expression in humans and rats, and dysfunction of 
      Cx43 also induces depressive behaviors in rats and mice. Recently Cx43 has 
      received considerable critical attention and is highly implicated in the onset of 
      depression. However, the pathological mechanisms of depression-like behavior 
      associated with Cx43 still remain ambiguous. In this review we summarize the 
      recent progress regarding the underlying mechanisms of Cx43 in the etiology of 
      depression-like behaviors including gliotransmission, metabolic disorders, and 
      neuroinflammation. We also discuss the effects of antidepressants (monoamine 
      antidepressants and ketamine) on Cx43. The clarity of the candidate pathological 
      mechanisms of depression-like behaviors associated with Cx43 and its potential 
      pharmacological roles for antidepressants will benefit the exploration of a novel 
      antidepressant target.
CI  - (c) 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia 
      Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.
FAU - Zhang, Ning-Ning
AU  - Zhang NN
AD  - State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, 
      Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical 
      Sciences and Peking Union Medical College, Beijing, 100050, China.
FAU - Zhang, Yi
AU  - Zhang Y
AD  - Department of Anatomy, School of Chinese Medicine, Beijing University of Chinese 
      Medicine, Beijing, 102488, China.
FAU - Wang, Zhen-Zhen
AU  - Wang ZZ
AD  - State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, 
      Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical 
      Sciences and Peking Union Medical College, Beijing, 100050, China. 
      wangzz@imm.ac.cn.
FAU - Chen, Nai-Hong
AU  - Chen NH
AD  - State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, 
      Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical 
      Sciences and Peking Union Medical College, Beijing, 100050, China. 
      chennh@imm.ac.cn.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20220210
PL  - United States
TA  - Acta Pharmacol Sin
JT  - Acta pharmacologica Sinica
JID - 100956087
RN  - 0 (Antidepressive Agents)
RN  - 0 (Connexin 43)
RN  - 0 (Connexins)
RN  - 0 (Neurotransmitter Agents)
RN  - 690G0D6V8H (Ketamine)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/metabolism/pharmacology/therapeutic use
MH  - Astrocytes/metabolism
MH  - Connexin 43/metabolism
MH  - Connexins/metabolism
MH  - Depression/drug therapy
MH  - *Depressive Disorder, Major/drug therapy
MH  - Humans
MH  - *Ketamine/pharmacology
MH  - Mice
MH  - Neurotransmitter Agents/metabolism
MH  - Prefrontal Cortex/metabolism
MH  - Rats
PMC - PMC9525669
OTO - NOTNLM
OT  - ATP
OT  - Ca2+ wave
OT  - Connexin 43
OT  - antidepressant target
OT  - astrocyte
OT  - depression
OT  - hippocampus
OT  - prefrontal cortex
COIS- The authors declare no competing interests.
EDAT- 2022/02/12 06:00
MHDA- 2022/10/05 06:00
PMCR- 2023/10/01
CRDT- 2022/02/11 05:35
PHST- 2021/08/30 00:00 [received]
PHST- 2022/01/06 00:00 [accepted]
PHST- 2022/02/12 06:00 [pubmed]
PHST- 2022/10/05 06:00 [medline]
PHST- 2022/02/11 05:35 [entrez]
PHST- 2023/10/01 00:00 [pmc-release]
AID - 10.1038/s41401-022-00861-2 [pii]
AID - 861 [pii]
AID - 10.1038/s41401-022-00861-2 [doi]
PST - ppublish
SO  - Acta Pharmacol Sin. 2022 Oct;43(10):2448-2461. doi: 10.1038/s41401-022-00861-2. 
      Epub 2022 Feb 10.