Time-dependent miR-16 serum fluctuations together with reciprocal changes in the expression level of miR-16 in mesocortical circuit contribute to stress resilient phenotype in chronic mild stress – An animal model of depression

Żurawek, Dariusz; Kuśmider, Maciej; Faron-Górecka, Agata; Gruca, Piotr; Pabian, Paulina; Kolasa, Magdalena; Solich, Joanna; Szafran-Pilch, Kinga; Papp, Mariusz; Dziedzicka-Wasylewska, Marta

doi:10.1016/j.euroneuro.2015.11.013

Cited by 37 publications

(28 citation statements)

References 52 publications

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“…A reduction of sucrose consumption reflects anhedonia, which is one of the core symptoms of depression [21]. And this change could be restored by antidepressant treatment [22, 23]. The same results were found after HJDT treatment in FST.…”

Section: Discussionmentioning

confidence: 64%

Huanglian‐Jie‐Du‐Tang Extract Ameliorates Depression‐Like Behaviors through BDNF‐TrkB‐CREB Pathway in Rats with Chronic Unpredictable Stress

Zhong

Liu

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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Neuroinflammation is considered as one of the common pathogeneses of depression. Huanglian-Jie-Du-Tang (HJDT) is a traditional Chinese herbal formula. The present study investigates the antidepressant-like effect of HJDT and its possible mechanism in rats. Rats were given HJDT (2, 4, and 8 g/kg, intragastrically), paroxetine (1.8 mg/kg, intragastrically), or an equivalent volume of saline for 42 days. The depression-related behaviors, including sucrose preference test (SPT), open field test (OFT), novel objective recognition task (NORT), and forced swimming test (FST), were detected. 5-Hydroxytryptamine (5-HT) and dopamine (DA) contents, microglial activation, proinflammatory cytokines, and brain derived neurotrophic factor (BDNF), tropomyosin receptor kinases B (TrkB), and cAMP-responsive element binding protein (CREB) expression were investigated. The results indicated HJDT (2 and 4 g/kg) dramatically ameliorated the depression-like behaviors. Also HJDT decreased the number of microglia and the proinflammatory cytokines in hippocampus. Western-blotting analysis displayed HJDT upregulated BDNF, TrkB, and pCREB/CREB expression in hippocampus. Particularly, pCREB DNA activity enhanced with HJDT treatment in hippocampus. But there was no difference in the 5-HT and DA contents with HJDT treatment. In conclusion, it was supposed that HJDT might be a potential Chinese medicine decoction for treating or alleviating complex symptoms of depression through BDNF-TrkB-CREB pathway.

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Section: Discussionmentioning

confidence: 64%

Huanglian‐Jie‐Du‐Tang Extract Ameliorates Depression‐Like Behaviors through BDNF‐TrkB‐CREB Pathway in Rats with Chronic Unpredictable Stress

Zhong

Liu

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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“…Moreover, it has been discovered that miR-16 up-regulation and BNDF down-regulation play a role in the development of depression-like behaviors in the hippocampus (Bai et al, 2012) and miR-16 can also regulate multiple serotonergic pathway-related genes (Moya et al, 2013). According to previous studies, there was a decrease of CSF miR-16 in MDD but an increase of serum miR-16 after CUMS (Song et al, 2015; Zurawek et al, 2016). This study injected miR-16 into the raphe nucleus and observed a significant attenuation of depressive like behaviors, in fact as effective as Fluoxetine treatment.…”

Section: Discussionmentioning

confidence: 82%

“…miRNAs are highly conserved among mammals, therefore study results can be well applied to humans, and thus beneficial for the development of clinical drugs (Zurawek et al, 2016). Recently, the potential role of regulatory apoptosis and autophagy in neurodegenerative diseases and tumor suppression has been widely investigated (Polajnar and Zerovnik, 2014).…”

Section: Introductionmentioning

confidence: 99%

miR-16 and Fluoxetine Both Reverse Autophagic and Apoptotic Change in Chronic Unpredictable Mild Stress Model Rats

Yang

et al. 2017

Front. Neurosci.

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In the clinic selective serotonin reuptake inhibitors (SSRIs), like Fluoxetine, remain the primary treatment for major depression. It has been suggested that miR-16 regulates serotonin transporters (SERT) via raphe nuclei and hippocampal responses to antidepressants. However, the underlying mechanism and regulatory pathways are still obtuse. Here, a chronic unpredicted mild stress (CUMS) depression model in rats was established, and then raphe nuclei miR-16 and intragastric Fluoxetine injections were administered for a duration of 3 weeks. An open field test and sucrose preference quantification displayed a significant decrease in the CUMS groups when compare to the control groups, however these changes were attenuated by both miR-16 and Fluoxetine treatments. A dual-luciferase reporter assay system verified that hsa-miR-16 inhibitory effects involve the targeting of 3′UTR on the 5-HTT gene. Expression levels of miR-16 and BDNF in the hippocampus were examined with RT-PCR, and it was found that increased 5-HT2a receptor expression induced by CUMS can be decreased by miR-16 and Fluoxetine administration. Immunofluorescence showed that expression levels of neuron NeuN and MAP-2 in CUMS rats were lower. Apoptosis and autophagy levels were evaluated separately through relative expression of Bcl-2, Caspase-3, Beclin-1, and LC3II. Furthermore, CUMS was found to decrease levels of hippocampal mTOR, PI3K, and AKT. These findings indicate that apoptosis and autophagy related pathways could be involved in the effectiveness of antidepressants, in which miR-16 participates in the regulation of, and is likely to help integrate rapid therapeutic strategies to alleviate depression clinically. These findings indicate that miR-16 participates in the regulation of apoptosis and autophagy and could account for some part of the therapeutic effect of SSRIs. This discovery has the potential to further the understanding of SSRIs and accelerate the development of new treatments for depression.

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“…The observed fluctuations were observed not only at the level of receptors or neuropeptides but also at the microRNA (miRNA) level. Using the CMS protocol and studying the differences between stress-reactive and stress-resilient groups of animals, we observed fluctuations in miRNA 16 depending on the duration of the stress stimuli (Żurawek et al 2016). It appears that the CMS model reflects the dynamic process of the brain response to stressful stimuli, which can further contribute to the development of depression.…”

Section: Discussionmentioning

confidence: 99%

Regulation of somatostatin receptor 2 in the context of antidepressant treatment response in chronic mild stress in rat

et al. 2018

Self Cite

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RationaleThe role of somatostatin and its receptors for the stress-related neuropsychiatric disorders has been widely raised. Recently, we have also demonstrated the involvement of somatostatin receptor type 2-sst2R and dopamine receptor type 2-D2R in stress.ObjectiveIn this context, we decided to find if these receptors are involved in response to antidepressant treatment in animal model of depression—chronic mild stress (CMS).MethodsHere, we report data obtained following 7-week CMS procedure. The specific binding of [125I]Tyr3-Octreotide to sst2R and [3H]Domperidone to D2R was measured in the rat brain, using autoradiography. Additionally, the level of dopamine and metabolites was measured in the rat brain.ResultsIn the final baseline test after 7 weeks of stress, the reduced consumption of sucrose solution was observed (controls vs the stressed animals (6.25 0.16 vs. 10.39 0.41; p < 0.05). Imipramine was administered for the next 5 weeks, and it reversed anhedonia in majority of animals (imipramine-reactive); however, in some animals, it did not (imipramine-non-reactive). Two-way repeated measures ANOVA revealed significant effects of stress and treatment and time interaction [F(16, 168) = 3.72; p < 0.0001], n = 10 per groups. We observed decreased binding of [125I]Tyr3-Octreotide in most of rat brain regions in imipramine non-reactive groups of animals. The decrease of D2R after stress in striatum and nucleus accumbens and no effect of imipramine were observed.In the striatum and prefrontal cortex, the significant role of stress and imipramine in dopamine levels was observed.ConclusionsThe results obtained in binding assays, together with dopamine level, indicate the involvement of sst2R receptors for reaction to antidepressant treatment. Besides, the stress context itself changes the effect of antidepressant drug.

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Time-dependent miR-16 serum fluctuations together with reciprocal changes in the expression level of miR-16 in mesocortical circuit contribute to stress resilient phenotype in chronic mild stress – An animal model of depression

Cited by 37 publications

References 52 publications

Huanglian‐Jie‐Du‐Tang Extract Ameliorates Depression‐Like Behaviors through BDNF‐TrkB‐CREB Pathway in Rats with Chronic Unpredictable Stress

Huanglian‐Jie‐Du‐Tang Extract Ameliorates Depression‐Like Behaviors through BDNF‐TrkB‐CREB Pathway in Rats with Chronic Unpredictable Stress

miR-16 and Fluoxetine Both Reverse Autophagic and Apoptotic Change in Chronic Unpredictable Mild Stress Model Rats

Regulation of somatostatin receptor 2 in the context of antidepressant treatment response in chronic mild stress in rat

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