Calhm2 governs astrocytic ATP releasing in the development of depression-like behaviors

Jun, Michael; Xiaolong, Q; Chaojuan, Y; Peng, Rui-yuan; Shukun, W; Junbing, W; Li, H; Hong, Can; Jin-bo, Cui; Rong, Weining; Yajin, L; Lanqun, M; Fengchao, W; Zhiying, W; Jianxiong, A; Yun, Weiwen; Xia, Zian; Chen, Zhuoran; Zengqiang, Y

doi:10.1038/mp.2017.229

Cited by 74 publications

(74 citation statements)

References 43 publications

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“…The combination of non-specific P2 receptor antagonists with antidepressants has been associated with significant antidepressant-like effects in animal models [58]. It has been hypothesized that ATP released from astrocytes might trigger the development of depressive-like behaviors [59,60]. ATP-mediated signaling through the P2X7 receptor subtype seems to play an important role in depression [54][55][56].…”

Section: Atp and Depressionmentioning

confidence: 99%

Purinergic Signaling and Related Biomarkers in Depression

et al. 2020

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It is established that purinergic signaling can shape a wide range of physiological functions, including neurotransmission and neuromodulation. The purinergic system may play a role in the pathophysiology of mood disorders, influencing neurotransmitter systems and hormonal pathways of the hypothalamic-pituitary-adrenal axis. Treatment with mood stabilizers and antidepressants can lead to changes in purinergic signaling. In this overview, we describe the biological background on the possible link between the purinergic system and depression, possibly involving changes in adenosine- and ATP-mediated signaling at P1 and P2 receptors, respectively. Furthermore, evidence on the possible antidepressive effects of non-selective adenosine antagonist caffeine and other purinergic modulators is reviewed. In particular, A2A and P2X7 receptors have been identified as potential targets for depression treatment. Preclinical studies highlight that both selective A2A and P2X7 antagonists may have antidepressant effects and potentiate responses to antidepressant treatments. Consistently, recent studies feature the possible role of the purinergic system peripheral metabolites as possible biomarkers of depression. In particular, variations of serum uric acid, as the end product of purinergic metabolism, have been found in depression. Although several open questions remain, the purinergic system represents a promising research area for insights into the molecular basis of depression.

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Section: Atp and Depressionmentioning

confidence: 99%

Purinergic Signaling and Related Biomarkers in Depression

et al. 2020

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“…WARS may partially promote the growth of UM cells by activating the PI3K/AKT signaling pathway, thereby accelerating tumor development [44]. In addition to EDNRB and WARS, the remaining 19 genes showing evidence interacting in the progress of various types of cancer [50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68], but left few traces showing the connection with UM prognosis in the previous research. https://doi.org/10.1371/journal.pone.0242263.g004…”

Section: Plos Onementioning

confidence: 99%

Identification of prognostic genes in uveal melanoma microenvironment

Luo

2020

PLoS ONE

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Background Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Many previous studies have demonstrated that the infiltrating of immune and stromal cells in the tumor microenvironment contributes significantly to prognosis. Methods Dataset TCGA-UVM, download from TCGA portal, was taken as the training cohort, and GSE22138, obtained from GEO database, was set as the validation cohort. ESTIMATE algorithm was applied to find intersection differentially expressed genes (DEGs) among tumor microenvironment. Kaplan-Meier analysis and univariate Cox regression model were performed on intersection DEGs to initial screen for potential prognostic genes. Then these genes entered into the validation cohort for validation using the same methods as that in the training cohort. Moreover, we conducted correlation analyses between the genes obtained in the validation cohort and the status of chromosome 3, chromosome 8q, and tumor metastasis to get prognosis genes. At last, the immune infiltration analysis was performed between the prognostic genes and 6 main kinds of tumor-infiltrating immune cells (TICs) for understanding the role of the genes in the tumor microenvironment. Results 959 intersection DEGs were found in the UM microenvironment. Kaplan-Meier and Cox analysis was then performed in the training and validation cohorts on these DEGs, and 52 genes were identified with potential prognostic value. After comparing the 52 genes to chromosome 3, chromosome 8q, and metastasis, we obtained 21 genes as the prognostic genes. The immune infiltration analysis showed that Neutrophil had the potential prognostic ability, and almost every prognostic gene we had identified was correlated with abundances of Neutrophil and CD8+ T Cell. Conclusions Identifying 21 prognosis genes (SERPINB9, EDNRB, RAPGEF3, HFE, RNF43, ZNF415, IL12RB2, MTUS1, NEDD9, ZNF667, AZGP1, WARS, GEM, RAB31, CALHM2, CA12, MYEOV, CELF2, SLCO5A1, ISM1, and PAPSS2) could accurately identify patients' prognosis and had close interactions with Neutrophil in the tumor environment, which may provide UM patients with personalized prognosis prediction and new treatment insights.

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“…Further work on the regulation of extracellular ATP established Calhm2 (Calcium Homeostasis Modulator Family Member 2) as an ATP‐releasing channel in astrocytes. Loss of Calhm2 in the hippocampus of mice was sufficient to produce depression‐related behaviors, accompanied by reduced spine density and neuronal activity . In both studies, restoring physiological ATP levels had a rapid antidepressant‐like effect.…”

Section: Model Of Cd39 Function In Stress Copingmentioning

confidence: 87%

“…We now consider MDD as a highly complex and heterogeneous disorder, with alterations in synapse formation and plasticity, neurogenesis, and inflammation being involved in its pathophysiology [2].Recently, insufficient release of ATP by astrocytes was linked to chronic stressinduced depressive-like behaviors of mice [3]. Further work on the regulation of extracellular ATP established Calhm2 (Calcium Homeostasis Modulator Family Member 2) as an ATP-releasing channel in astrocytes.Loss of Calhm2 in the hippocampus of mice was sufficient to produce depression-related behaviors, accompanied by reduced spine density and neuronal activity [4]. In both studies, restoring physiological ATP levels had a rapid antidepressant-like effect.…”

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confidence: 82%

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Depression: a new enzyme AT play

Martins

Schratt

2020

EMBO Reports

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Neuronal activity is the main contributor to the high‐energy demand of the human brain. ATP is needed for the maintenance of ionic gradients, neurotransmitter transport, and release, as well as the signaling pathways that follow activation of post‐synaptic receptors. The inability to maintain a high supply of ATP through tight regulatory mechanisms can, therefore, have severe consequences for brain function. In this issue of EMBO Reports, Cui et al [1] show that pharmacological inhibition or genetic inactivation of CD39, an ectonucleotide tri(di)phosphohydrolase responsible for converting ATP into AMP, has antidepressant‐like effects by maintaining high extracellular ATP levels in the presence of stress.

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Calhm2 governs astrocytic ATP releasing in the development of depression-like behaviors

Cited by 74 publications

References 43 publications

Purinergic Signaling and Related Biomarkers in Depression

Purinergic Signaling and Related Biomarkers in Depression

Identification of prognostic genes in uveal melanoma microenvironment

Depression: a new enzyme AT play

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