scholarly journals Stimulation of sigma-1 receptor ameliorates depressive-like behaviors via mitochondrial ATP production in CaMKIV null mice

2016 ◽  
Vol 147 (4) ◽  
pp. 206-210
Author(s):  
Shigeki Moriguchi ◽  
Kohji Fukunaga
Keyword(s):  
Sigma 1 Receptor ◽  
Atp Production ◽  
Sigma 1 ◽  
Stimulation Of

scholarly journals Chronic stimulation of the sigma-1 receptor ameliorates autonomic nerve dysfunction and atrial fibrillation susceptibility in a rat model of depression

2018 ◽  
Vol 315 (6) ◽  
pp. H1521-H1531 ◽  
Author(s):  
Xin Liu ◽  
Chuan Qu ◽  
Hongjie Yang ◽  
Shaobo Shi ◽  
Cui Zhang ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Sympathetic Activity ◽  
Autonomic Nerve ◽  
Electrical Remodeling ◽  
Intragastric Administration ◽  
Chronic Stimulation ◽  
Sigma 1 Receptor ◽  
Sigma 1 ◽  
Nerve Dysfunction ◽  
Stimulation Of

The present study aimed to assess the effect of sigma-1 receptor (S1R) stimulation on autonomic nerve dysfunction and susceptibility to atrial fibrillation (AF) in a rat depression model. Male rats were randomly divided into one of the following four treatment groups: saline [control (CTL)]; saline + intragastric administration of SA4503, an agonist of S1R (CTS); chronic unpredictable mild stress (CUMS) to produce depression (MDD); and CUMS + intragastric administration of SA4503 (MDS). Depression-like behaviors, such as reduced sucrose preference, decreased body weight gain, and increased immobility time during forced swimming, improved in the MDS group after 4 wk of SA4503 treatment. Compared with rats in the CTL group, rats in the MDD group showed significantly augmented sympathetic activity, reduced parasympathetic activity, decreased heart rate variability, and lowered S1R expression in the atrium and hippocampus (all P < 0.01). However, rats in the MDS group showed mitigated aforementioned alterations and improved electrical remodeling compared with rats in the MDD group (all P < 0.01). Furthermore, rats in the MDS group showed shortened activation latencies, increased effective refractory periods, and lowered frequency of AF incidence duration and fibrosis compared with rats in the MDD group (all P < 0.01). The results indicate that S1R stimulation reduces sympathetic activity and susceptibility to AF by improving depressive behaviors, modulating cardiac autonomic nerve balance, lightening nerve remodeling, and upregulating S1R and ion channel protein expression. NEW & NOTEWORTHY Chronic stimulation of the sigma-1 receptor (S1R) ameliorates depression-induced autonomic nerve dysfunction by modulating the imbalance between overactivated sympathetic activity and decreased vagal activity. Chronic S1R stimulation alleviates atrial electrical remodeling, fibrosis, and susceptibility to atrial fibrillation (AF). The S1R agonist may target the underlying mechanisms related to AF occurrence. The results indicate that the S1R could be a potential clinical target for atrial arrhythmia, especially when it is combined with major depressive disorders.

Stimulation of Sigma-1 Receptor Ameliorates Depressive-like Behaviors in CaMKIV Null Mice

2014 ◽  
Vol 52 (3) ◽  
pp. 1210-1222 ◽  
Author(s):  
Shigeki Moriguchi ◽  
Hiroyuki Sakagami ◽  
Yasushi Yabuki ◽  
Yuzuru Sasaki ◽  
Hisanao Izumi ◽  
...  
Keyword(s):  
Sigma 1 Receptor ◽  
Sigma 1 ◽  
Stimulation Of

scholarly journals Stimulation of the Sigma-1 Receptor by DHEA Enhances Synaptic Efficacy and Neurogenesis in the Hippocampal Dentate Gyrus of Olfactory Bulbectomized Mice

PLoS ONE ◽  
2013 ◽  
Vol 8 (4) ◽  
pp. e60863 ◽  
Author(s):  
Shigeki Moriguchi ◽  
Yasuharu Shinoda ◽  
Yui Yamamoto ◽  
Yuzuru Sasaki ◽  
Kosuke Miyajima ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Synaptic Efficacy ◽  
Hippocampal Dentate Gyrus ◽  
Sigma 1 Receptor ◽  
Sigma 1 ◽  
Stimulation Of

scholarly journals Stimulation of Sigma-1 Receptor Protects against Cardiac Fibrosis by Alleviating IRE1 Pathway and Autophagy Impairment

2021 ◽  
Vol 2021 ◽  
pp. 1-25
Author(s):  
Jing Qu ◽  
Miaoling Li ◽  
Dongxu Li ◽  
Yanguo Xin ◽  
Junli Li ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Er Stress ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Cardiac Fibroblast ◽  
Autophagic Flux ◽  
Sigma 1 Receptor ◽  
Fibroblast Activation ◽  
Sigma 1 ◽  
Stimulation Of

Sigma-1 receptor (Sig1R), a chaperone in the endoplasmic reticulum (ER) membrane, has been implicated in cardiac hypertrophy; however, its role in cardiac fibroblast activation has not been established. This study investigated the possible association between Sig1R and this activation by subjecting mice to sham, transverse aortic constriction (TAC), and TAC plus fluvoxamine (an agonist of Sig1R) treatments. Cardiac function and fibrosis were evaluated four weeks later by echocardiography and histological staining. In an in vitro study, neonatal rat cardiac fibroblasts were treated with fluvoxamine or NE-100 (an antagonist of Sig1R) in the presence or absence of transforming growth factor beta1 (TGF-β1). Fibrotic markers, ER stress pathways, and autophagy were then investigated by qPCR, western blotting, immunofluorescence, confocal microscopy, and transmission electron microscopy. Fluvoxamine treatment reduced cardiac fibrosis, preserved cardiac function, and attenuated cardiac fibroblast activation. Inhibition of the IRE1/XBP1 pathway, a branch of ER stress, by a specific inhibitor of IRE1 endonuclease activity, attenuated the pathological process. Fluvoxamine stimulation of Sig1R restored autophagic flux in cardiac fibroblasts, indicating that Sig1R appears to play a protective role in the activation of cardiac fibroblasts by inhibiting the IRE1 pathway and restoring autophagic flux. Sig1R may therefore represent a therapeutic target for cardiac fibrosis.

Abstract 249: Sigma-1 Receptor Agonist Ameliorates Mitochondrial ATP Production and Apoptosis in Cardiac Myocytes

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Hideaki Tagashira ◽  
Norifumi Shioda ◽  
Md. Shenuarin Bhuiyan ◽  
Kohji Fukunaga
Keyword(s):  
Selective Serotonin Reuptake Inhibitors ◽  
Intracellular Localization ◽  
Receptor Expression ◽  
Neonatal Rat ◽  
Cardiomyocyte Hypertrophy ◽  
Ang Ii ◽  
Receptor Stimulation ◽  
Sigma 1 Receptor ◽  
Atp Production ◽  
Sigma 1

Objective: Selective serotonin reuptake inhibitors (SSRIs) are known to reduce post-myocardial infarction (MI)-induced morbidity and mortality. However, the molecular mechanism underlying SSRI-induced cardioprotection remains unclear. We previous reported that fluvoxamine with high affinity for sigma-1 receptor ameliorates cardiac hypertrophy and dysfunction via sigma-1 receptor stimulation. In non-cardiomyocytes, sigma-1 receptor interacts with IP 3 receptor (IP 3 R), which may promote Ca 2+ transport to mitochondria. We here investigated the role of sigma-1 receptor for sarcoplasmic reticulum (SR)-mitochondrial Ca 2+ signaling in neonatal rat ventricular cardiomyocytes. Methods: Cultured cardiomyocytes were treated with angiotensin II (Ang II) during 72 hr followed by fluvoxamine and/or NE-100 treatment during the last 24 hr. Then, we investigated intracellular localization of sigma-1 receptor and IP 3 R. We also measured phenylephrine (PE)-induced mitochondrial Ca 2+ and cytosolic Ca 2+ mobilization and ATP content in Ang II-treated cardiomyocytes with or without fluvoxamine treatments. Results: Ang II stimulation for 72 hr elicited cardiomyocyte hypertrophy, downregulation of sigma-1 receptor expression and declined PE-induced Ca 2+ mobilization into cytosol and mitochondria. Fluvoxamine treatments restored sigma-1 receptor expression and PE-induced Ca 2+ mobilization into mitochondria. Moreover, fluvoxamine treatment completely restored Ang II-induced apoptosis. We also confirmed in vivo that fluvoxamine treatment rescue transverse aortic constriction-induced cardiac dysfunction and the reduced ATP concentration. Conclusions: These results suggested that fluvoxamine rescue cardiomyocytes from AngII-induced cardiac myocyte apoptosis through enhancement of SR-mitochondria Ca 2+ transport and mitochondrial ATP production via sigma-1 receptor stimulation.

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