Connexin 43: insights into candidate pathological mechanisms of depression and its implications in antidepressant therapy

Zhang, Ningning; Zhang, Yi; Wang, Zhenzhen; Chen, Nai‐Hong

doi:10.1038/s41401-022-00861-2

Cited by 17 publications

(18 citation statements)

References 172 publications

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“…From the available conclusions, HC opening appears to play a regulatory role in diverse brain diseases. A short-term opening increases cell fitness, while a long-term opening causes damage to cells [ 6 ]. The permeability of Cx43 HC to bromoethane (EtBr), a cellular uptake of the non-fluorescent permeable tracer, is a significant indicator reflecting the activity of HC.…”

Section: Association Between Cx43 and Inflammationmentioning

confidence: 99%

“…Ketamine exhibits anti-inflammatory properties and modulates the brain’s innate immune response [ 157 ]. Acute treatment with therapeutically relevant concentrations of ketamine inhibited the activity of Cx43 HCs, but not GJCs, possibly by inhibiting the release of TNF-α and IL-1β [ 6 ]. Because of the different results of the drug effect on Cx43, we can guess that the receptors and triggering pathways of different antidepressant drugs are not the same due to the specific mechanism.…”

Section: Cx43 As a Mediator Of Neuroinflammation And Depressionmentioning

confidence: 99%

“…Six connexin subunits form a connexon [ 5 ]. A GJC is formed by a pair of connexons in adjacent cell membranes, while uncoupled connexons exist as hemichannels (HCs) [ 6 ]. Gap junctions allow for communication between cells through ion exchange and small molecules acting as secondary messengers, such as calcium ions (Ca 2+ ), nicotinamide adenine dinucleotide, 1,4,5-trisphosphate receptors (IP3Rs), adenosine triphosphate (ATP), glutamate, and glucose [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

“…The opening of HCs under stress conditions is beneficial to increase the fitness of cells in the short term. Still, long-term activation might cause damage to cells, thereby causing the disease [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

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Connexin 43: An Interface Connecting Neuroinflammation to Depression

et al. 2023

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Major depressive disorder (MDD) is a leading chronic mental illness worldwide, characterized by anhedonia, pessimism and even suicidal thoughts. Connexin 43 (Cx43), mainly distributed in astrocytes of the brain, is by far the most widely and ubiquitously expressed connexin in almost all vital organs. Cx43 forms gap junction channels in the brain, which mediate energy exchange and effectively maintain physiological homeostasis. Increasing evidence suggests the crucial role of Cx43 in the pathogenesis of MDD. Neuroinflammation is one of the most common pathological features of the central nervous system dysfunctions. Inflammatory factors are abnormally elevated in patients with depression and are closely related to nearly all links of depression. After activating the inflammatory pathway in the brain, the release and uptake of glutamate and adenosine triphosphate, through Cx43 in the synaptic cleft, would be affected. In this review, we have summarized the association between Cx43 and neuroinflammation, the cornerstones linking inflammation and depression, and Cx43 abnormalities in depression. We also discuss the significant association of Cx43 in inflammation and depression, which will help to explore new antidepressant drug targets.

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Section: Association Between Cx43 and Inflammationmentioning

confidence: 99%

Section: Cx43 As a Mediator Of Neuroinflammation And Depressionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Connexin 43: An Interface Connecting Neuroinflammation to Depression

et al. 2023

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“…A host of studies revealed that Cx43 plays an important role in the process of depression, which could decrease the expression of Cx43 in human and rat [14][15][16]. Similarly, low expression of Cx43 induced depression in rat and mice [17]. Cx43 has the function of linking gap junctions with half connexins [18], and widely existed in nervous system.…”

Section: Introductionmentioning

confidence: 99%

Mahonia Alkaloids (MA) Ameliorate Depression Induced Gap Junction Dysfunction by miR-205/Cx43 Axis

Wei

et al. 2022

Neurochem Res

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Depression has become an important disease threatening human health. In recent years, the e cacy of Traditional Chinese Medicine (TCM) in treating the disease has become increasingly prominent, so it is meaningful to nd new antidepressant TCM. Mahonia fortune (Lindl.) Fedde is a primary drug in traditional formulas for the treatment of depression, however, the exact mechanism of its action is unclear. This study aimed to research the effect of MA on the improvement of gap junction function in depression via the miR-205/Cx43 pathway. The antidepressant effects of MA were observed by a rat model of reserpine-induced depression and a model of corticosterone (CORT)-induced astrocytes. The concentrations of neurotransmitters were measured by ELISA, the expression of Connexin 43 (Cx43) protein was measured by Immunohistochemistry, the expression of Cx43, BDNF, CREB proteins were measured by western-blot, the pathological changes of prefrontal cortex were observed by hematoxylineosin (H&E) staining. The binding of miR-205 and Cx43 was veri ed with a Luciferase reporter gene. Gap junction dysfunction detected by uorescent yellow staining. The results con rmed that MA remarkably decreased miR-205 expression and increased Cx43, BDNF, CREB expression in depression rat and CORTinduced astrocytes. In addition, after overexpression of miR-205 in vitro, MA signi cantly increased Cx43, BDNF and CREB expression in CORT-induced astrocytes. Thus, MA may target Cx43 through miR-205 to regulate CREB/BDNF signaling pathway to improve depressive behavior. Highlights Mahonia alkaloids (MA) ameliorate depression-like behavior of rats. MA ameliorate depression-like behavior by down-regulating miR-205 expression. GJA1 (Cx43) is a target gene of miR-205. MA regulate Cx43 protein. MA activate CREB/BDNF pathway to improve depression-like behavior through miR-205/Cx43.

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Adipogenic differentiation effect of human periodontal ligament stem cell initial cell density on autologous cells and human bone marrow stromal cells

Wang,

Gu,

Sun

et al. 2024

Cell Biochemistry & Function

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Stem cells demonstrate differentiation and regulatory functions. In this discussion, we will explore the impacts of cell culture density on stem cell proliferation, adipogenesis, and regulatory abilities. This study aimed to investigate the impact of the initial culture density of human periodontal ligament stem cells (hPDLSCs) on the adipogenic differentiation of autologous cells. Our findings indicate that the proliferation rate of hPDLSCs increased with increasing initial cell density (0.5–8 × 104 cells/cm2). After adipogenic differentiation induced by different initial cell densities of hPDLSC, we found that the mean adipose concentration and the expression levels of lipoprotein lipase (LPL), CCAAT/enhancer binding protein α (CEBPα), and peroxisome proliferator‐activated receptor γ (PPAR‐γ) genes all increased with increasing cell density. To investigate the regulatory role of hPDLSCs in the adipogenic differentiation of other cells, we used secreted exocrine vesicles derived from hPDLSCs cultivated at different initial cell densities of 50 μg/mL to induce the adipogenic differentiation of human bone marrow stromal cells. We also found that the mean adipose concentration and expression of LPL, CEBPα, and PPARγ genes increased with increasing cell density, with an optimal culture density of 8 × 104 cells/cm2. This study provides a foundation for the application of adipogenic differentiation in stem cells.

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Connexin 43: insights into candidate pathological mechanisms of depression and its implications in antidepressant therapy

Cited by 17 publications

References 172 publications

Connexin 43: An Interface Connecting Neuroinflammation to Depression

Connexin 43: An Interface Connecting Neuroinflammation to Depression

Mahonia Alkaloids (MA) Ameliorate Depression Induced Gap Junction Dysfunction by miR-205/Cx43 Axis

Adipogenic differentiation effect of human periodontal ligament stem cell initial cell density on autologous cells and human bone marrow stromal cells

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