Nitric Oxide and Cyclic Guanosine Monophosphate Signaling Mediates the Antidepressant Effects of Acupuncture in the Rat Model of Chronic Unpredictable Mild Stress

The current study aimed to investigate the effects and mechanisms of electroacupuncture (EA) treatment applied to Bai hui (GV20) and Yin tang (GV29) acupoints (1 mA, 2 Hz, continuous wave, 20 minutes) for 28 days in a rat model of chronic unpredictable mild stress (CUMS) on reuptake of serotonin (5-hydroxytryptamine (5-HT)) and miRNA-16 levels in the hippocampus and serum. Rats were housed in individual cages, and CUMS was used to establish a rat model of depression. After EA treatment for 4 weeks, behavioral changes and indices including 5-HT transporter (SERT), 5-HT, and miRNA-16 levels in the hippocampus and serum were examined. The EA treatment significantly improved base levels of sucrose preference and exploratory behavior and significantly decreased SERT protein and mRNA expression in the hippocampus of depressed rats. Significantly increased 5-HT levels were observed, and miRNA-16 levels were significantly decreased in the hippocampus and serum of depressed rats. In conclusion, the antidepressant effects of EA treatment may be affected via inhibition of 5-HT reuptake, upregulation of 5-HT levels, and inhibition of miRNA-16 expression in the hippocampus and serum.

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Exploring the potential role of sonic hedgehog cell signalling pathway in antidepressant effects of nicotine in chronic unpredictable mild stress rat model

Heliyon ◽

10.1016/j.heliyon.2019.e01600 ◽

2019 ◽

Vol 5 (5) ◽

pp. e01600 ◽

Cited By ~ 2

Author(s):

Mohd Tayyab ◽

Mehdi H. Shahi ◽

Shirin Farheen ◽

Mubeena Mariyath P.M. ◽

Nabeela Khanam ◽

...

Keyword(s):

Sonic Hedgehog ◽

Rat Model ◽

Potential Role ◽

Cell Signalling ◽

Signalling Pathway ◽

Mild Stress ◽

Chronic Unpredictable Mild Stress ◽

Antidepressant Effects ◽

Cell Signalling Pathway

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Helicid Reverses the Effect of Overexpressing NCALD, Which Blocks the sGC/cGMP/PKG Signaling Pathway in the CUMS-Induced Rat Model

Journal of Healthcare Engineering ◽

10.1155/2021/7168397 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Xiao-Tong Zhang ◽

Yuan Zhang ◽

Yuan-Xiang Zhang ◽

Zhen-Yi Jiang ◽

Hui Yang ◽

...

Keyword(s):

Signaling Pathway ◽

Western Blotting ◽

Rat Model ◽

Caspase 3 ◽

Underlying Mechanism ◽

Mild Stress ◽

Chronic Unpredictable Mild Stress ◽

Adeno Associated Virus ◽

Protein Levels ◽

Antidepressant Effects

Background. Increasing evidence has shown that apoptosis in the hippocampus is closely related to depressive-like behavior. We previously reported that helicid had good antidepressant activities, which manifested as the alleviation of depression-like behaviors and the reversal of the high expression of neurocalcin delta (NCALD) in chronic unpredictable mild stress (CUMS) rats. The aim of this study was, therefore, to characterize the antidepressant-like effects and underlying mechanism of helicid on CUMS rats by silencing NCALD and using rescue experiments. Methods. We developed the CUMS rat model using CUMS stimulation from week 0 to week 6. The rats were treated with helicid, or NCALD silenced, then we overexpressed NCALD using adeno-associated virus. We also measured the protein levels of sGCα1, sGCβ1, PKG1/2, and cleaved caspase-3 in hippocampal tissues using western blotting and measured cGMP using an ELISA. Results. Treating CUMS rats by silencing NCALD or by the administration of helicid improved the depressive-like behavior. The levels of proteins, including sGC, PKG, cleaved caspase-3, and cGMP, in hippocampus all decreased. NCALD overexpression reversed these decreases and reversed the alleviation of depression-like behaviors in CUMS rats. Limitation. We only detected the antidepressant effects of helicid in the hippocampus; therefore, other parts of brain should also be studied. Conclusions. Inhibition of NCALD, as well as helicid administration, alleviated antidepressant-like behavior by regulating the expressions of apoptotic cytokines and the sGC/cGMP/PKG signaling pathway. Overexpressing NCALD reversed the amelioration effects of silenced NCALD and helicid administration.

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Cyclic Guanosine Monophosphate Modulates Locomotor Acceleration Induced by Nitric Oxide but not Serotonin in Clione limacina Central Pattern Generator Swim Interneurons

Integrative Organismal Biology ◽

10.1093/iob/obaa045 ◽

2020 ◽

Author(s):

Thomas J Pirtle ◽

Richard A Satterlie

Keyword(s):

Nitric Oxide ◽

Central Pattern Generator ◽

Guanylyl Cyclase ◽

Signal Transduction Pathway ◽

Soluble Guanylyl Cyclase ◽

Cyclic Guanosine Monophosphate ◽

Pattern Generator ◽

Guanosine Monophosphate ◽

Cellular Changes ◽

Clione Limacina

Abstract Typically, the marine mollusk, Clione limacina, exhibits a slow, hovering locomotor gait to maintain its position in the water column. However, the animal exhibits behaviorally relevant locomotor swim acceleration during escape response and feeding behavior. Both nitric oxide and serotonin mediate this behavioral swim acceleration. In this study, we examine the role that the second messenger, cGMP, plays in mediating nitric oxide and serotonin-induced swim acceleration. We observed that the application of an analog of cGMP or an activator of soluble guanylyl cyclase increased fictive locomotor speed recorded from Pd-7 interneurons of the animal’s locomotor central pattern generator. Moreover, inhibition of soluble guanylyl cyclase decreased fictive locomotor speed. These results suggest that basal levels of cGMP are important for slow swimming and that increased production of cGMP mediates swim acceleration in Clione. Because nitric oxide has its effect through cGMP signaling and because we show herein that cGMP produces cellular changes in Clione swim interneurons that are consistent with cellular changes produced by serotonin application, we hypothesize that both nitric oxide and serotonin function via a common signal transduction pathway that involves cGMP. Our results show that cGMP mediates nitric oxide-induced but not serotonin-induced swim acceleration in Clione.

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The nitric oxide–cGMP signaling pathway plays a significant role in tolerance to the analgesic effect of morphine

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y10-109 ◽

2011 ◽

Vol 89 (2) ◽

pp. 89-95 ◽

Cited By ~ 22

Author(s):

Ercan Ozdemir ◽

Ihsan Bagcivan ◽

Nedim Durmus ◽

Ahmet Altun ◽

Sinan Gursoy

Keyword(s):

Nitric Oxide ◽

Analgesic Effect ◽

Soluble Guanylate Cyclase ◽

Morphine Tolerance ◽

Cyclic Guanosine Monophosphate ◽

Guanosine Monophosphate ◽

Albino Rats ◽

Tail Flick ◽

Analgesic Effects ◽

Cgmp Signaling

Although the phenomenon of opioid tolerance has been widely investigated, neither opioid nor nonopioid mechanisms are completely understood. The aim of the present study was to investigate the role of the nitric oxide (NO)–cyclic guanosine monophosphate (cGMP) pathway in the development of morphine-induced analgesia tolerance. The study was carried out on male Wistar albino rats (weighing 180–210 g; n = 126). To develop morphine tolerance, animals were given morphine (50 mg/kg; s.c.) once daily for 3 days. After the last dose of morphine was injected on day 4, morphine tolerance was evaluated. The analgesic effects of 3-(5′-hydroxymethyl-2′-furyl)-1-benzylindazole (YC-1), BAY 41-2272, S-nitroso-N-acetylpenicillamine (SNAP), NG-nitro-l-arginine methyl ester (L-NAME), and morphine were considered at 15 or 30 min intervals (0, 15, 30, 60, 90, and 120 min) by tail-flick and hot-plate analgesia tests (n = 6 in each study group). The results showed that YC-1 and BAY 41-2272, a NO-independent activator of soluble guanylate cyclase (sGC), significantly increased the development and expression of morphine tolerance, and L-NAME, a NO synthase (NOS) inhibitor, significantly decreased the development of morphine tolerance. In conclusion, these data demonstrate that the nitric oxide–cGMP signal pathway plays a pivotal role in developing tolerance to the analgesic effect of morphine.

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