Effect of Buspirone, Fluoxetine and 8-OH-DPAT on Striatal Expression of Bax, Caspase-3 and Bcl-2 Proteins in 6-Hydroxydopamine-Induced Hemi-Parkinsonian Rats

Sharifi, Hamdollah; Nayebi, Alireza Mohajjel; Farajnia, Safar; Haddadi, Rasool

doi:10.15171/apb.2015.067

Cited by 13 publications

(5 citation statements)

References 31 publications

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“…Fluoxetine can increase the occurrence of hippocampal neurons in rats with depression, improve the stereology of synaptic structures, and restore the structure and function of the hippocampus [26]. Fluoxetine can reduce the expression of Bax mRNA in the hippocampus of rats with depression, increase the expression of Bcl-2 mRNA, and reduce neuronal apoptosis [27]. In summary, neuronal regeneration and apoptosis, neuroplasticity, BDNF, and related pathway regulation may be a common mechanism of antidepressants such as CSS and fluoxetine.…”

Section: Introductionmentioning

confidence: 99%

Antidepressant‐Like Effects and Cognitive Enhancement of Coadministration of Chaihu Shugan San and Fluoxetine: Dependent on the BDNF‐ERK‐CREB Signaling Pathway in the Hippocampus and Frontal Cortex

Yan

et al. 2020

BioMed Research International

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Background. Fluoxetine (FLU) is the first-line and widely used medication for depression; however, FLU treatment is almost ineffective in 30%-40% of patients with depression. In addition, there are some problems in FLU treatment, such as delayed efficacy, large side effects, and poor tolerance. Chaihu Shugan San (CSS) is a classic and effective antidepressant Chinese herbal medicine that has been used in China for thousands of years. CSS or coadministration of CSS and FLU has become one of the most recommended methods in the treatment of depression in China. However, the specific pathways of CSS and coadministration of CSS and FLU for antidepressant are still unclear. Objective. This study was designed to evaluate the antidepressant effects of CSS and coadministration of CSS and FLU. Methods. The chronic unpredictable mild stress (CUMS) rat model was used to simulate depression. 120 healthy adult male Sprague-Dawley (SD) rats were randomly divided into seven groups: the control group, CUMS group, low-dose CSS group, high-dose CSS group, FLU group, coadministration of low-dose CSS and FLU group, and coadministration of high-dose CSS and FLU group. The rats in different groups were given different interventions. Then, the depression-like behavior and cognitive function were evaluated by the sucrose preference test (SPT), forced swimming test (FST), open field test (OFT), and Y-maze test. What is more, the antidepressant mechanism of CSS and coadministration of CSS and FLU were studied through BDNF mRNA, ERK mRNA, CREB mRNA, BDNF, p-ERK/ERK, and p-CREB/CREB levels in the hippocampus and frontal cortex by Western blot and RT-PCR. Results. Compared with the CUMS group, CSS and coadministration of CSS and FLU could alleviate the depressive symptoms and improve cognitive function in CUMS rats (p<0.05); CSS and coadministration of CSS and FLU could increase the expression of BDNF, p-CREB/CREB, p-ERK/ERK, and BDNF mRNA, CREB mRNA, and ERK mRNA in the hippocampus and frontal cortex (p<0.05). Besides, the high-dose CSS combined with the fluoxetine group was significantly better than the fluoxetine group and CSS group (p<0.05). Discussion and Conclusion. Finally, we found that both CSS and coadministration of CSS and FLU play an antidepressant role, which may be due to the regulation of the BDNF/ERK/CREB signaling pathway in the hippocampus and frontal cortex. Among them, the coadministration of CSS and FLU can enhance the antidepressant effect of CSS or FLU alone, and the underlying mechanism needs further investigation.

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Section: Introductionmentioning

confidence: 99%

Antidepressant‐Like Effects and Cognitive Enhancement of Coadministration of Chaihu Shugan San and Fluoxetine: Dependent on the BDNF‐ERK‐CREB Signaling Pathway in the Hippocampus and Frontal Cortex

Yan

et al. 2020

BioMed Research International

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“…Apoptosis is an active programmed cell death which is initiated by different signaling pathways or organelle damage (Elmore, 2007;Gronbeck et al, 2016). Bcl-2 family include anti-apoptotic and pro-apoptotic proteins (Bcl-2 and BAX, respectively) which either inhibit or promote apoptosis by regulating the permeability of the mitochondrial outer membrane (Sharifi, Mohajjel Nayebi, Farajnia, & Haddadi, 2015). Bcl-2 is a strong anti-apoptotic protein and its overexpression leads to resistance of the cells to oxidative stress-induced apoptosis (Brunelle & Letai, 2009).…”

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confidence: 99%

Cerebrolysin attenuates ethanol-induced spatial memory impairments through inhibition of hippocampal oxidative stress and apoptotic cell death in rats

Vaghef

Farajdokht

Erfani

et al. 2019

Alcohol

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“…In its activated form, cleaved caspase-3 mediates apoptosis. Suppressed caspase-3 activation indirectly indicates suppressed apoptosis, which may suppress PD development through neuroprotection (Liu et al, 2013;Sharifi et al, 2015). Caspase-3 knockout enhances the anti-MPTP neurotoxic effects in mice (Yamada et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Compound Dihuang Granule Inhibits Nigrostriatal Pathway Apoptosis in Parkinson’s Disease by Suppressing the JNK/AP-1 Pathway

et al. 2021

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Compound Dihuang Granule (CDG) is widely used in traditional Chinese medicine (TCM) for the treatment of Parkinson’s disease (PD). It has been shown to alleviate PD symptoms. However, the molecular mechanisms of its action have not been established. To establish the molecular mechanisms of CDG against PD, we used TCM network pharmacology methods to predict its molecular targets and signaling pathways, followed by experimental validation. The Core Protein protein interaction (PPI) network of the 150 intersections between CDG and PD-related genes, comprising 23 proteins, including CASP3 (caspase-3), MAPK8 (JNK), FOS (c-Fos), and JUN (c-Jun). KEGG and GO analyses revealed that apoptotic regulation and MAPK signaling pathways were significantly enriched. Since c-Jun and c-Fos are AP-1 subunits, an important downstream JNK effector, we investigated if the JNK/AP-1 pathway influences CDG against apoptosis through the nigrostriatal pathways in PD rat models. Molecular docking analysis found that the top three bioactive compounds exhibiting the highest Degree Centrality following online database and LC-MS analysis had high affinities for JNK. Experimental validation analysis showed that CDG decreased the number of rotating laps and suppressed the levels of phosphorylated c-Jun, c-Fos, and JNK, as well as the number of TUNEL positive cells and the cleaved caspase-3 level in the nigrostriatal pathway. Furthermore, CDG treatment elevated the number of TH neurons, TH expression level, and Bcl-2/Bax protein ratio in a 6-OHDA-induced PD rat. These findings are in tandem with those obtained using SP600125, a specific JNK inhibitor. In conclusion, CDG suppresses the apoptosis of the nigrostriatal pathway and relieves PD symptoms by suppressing the JNK/AP-1 signaling pathway.

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Effect of Buspirone, Fluoxetine and 8-OH-DPAT on Striatal Expression of Bax, Caspase-3 and Bcl-2 Proteins in 6-Hydroxydopamine-Induced Hemi-Parkinsonian Rats

Cited by 13 publications

References 31 publications

Antidepressant‐Like Effects and Cognitive Enhancement of Coadministration of Chaihu Shugan San and Fluoxetine: Dependent on the BDNF‐ERK‐CREB Signaling Pathway in the Hippocampus and Frontal Cortex

Antidepressant‐Like Effects and Cognitive Enhancement of Coadministration of Chaihu Shugan San and Fluoxetine: Dependent on the BDNF‐ERK‐CREB Signaling Pathway in the Hippocampus and Frontal Cortex

Cerebrolysin attenuates ethanol-induced spatial memory impairments through inhibition of hippocampal oxidative stress and apoptotic cell death in rats

Compound Dihuang Granule Inhibits Nigrostriatal Pathway Apoptosis in Parkinson’s Disease by Suppressing the JNK/AP-1 Pathway

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