microRNA and mRNA profiles in the amygdala are associated with stress-induced depression and resilience in juvenile mice

Shen, Mengmeng; Song, Zhenhua; Wang, Jinhui

doi:10.1007/s00213-019-05209-z

Cited by 32 publications

(26 citation statements)

References 93 publications

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“…How microRNA-15a, microRNA-19b and microRNA-15b-5p in the amygdala and nucleus accumbens coordinately lead to major depression remains to be investigated. Moreover, numerous microRNAs and mRNAs in the nucleus accumbens, amygdala and ventral tegmental area are associated with depression-like behavior (24,25,27). How these microRNAs and mRNAs relevant to synapses and neural signaling pathways among these brain areas coordinately induce major depression remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

“…Mice lived in inescapable stressful environment constantly experienced defeated outcomes. Some mice showed depression-like symptoms like anhedonia and low self-esteem after exposure to CUMS, which induce repetitive negative memory that driven the mice to feel cognitive disability and emotional frustration (13,24,25,27,66,94,95). The paradigms of 3 week CUMS consisted of social isolation, empty cage, tilted cage, wet sawdust cage, white noise, restraint, circadian disturbance and strobe light (22,55,62,88).…”

Section: The Mouse Model Of Major Depression Induced By Chronic Unprementioning

confidence: 99%

“…The elucidation of endogenous mechanisms underlying major depression versus resilience should shed light on developing therapeutic strategies to convert depression into resilience. Recently, epigenetic process is thought to be a key switch from chronic stress to cellular and molecular pathology of major depression and resilience, especially microRNA (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28). As microRNA interacts with mRNA, by which the binding of microRNAs with their dicers degrade mRNAs and weaken their translation (29)(30)(31)(32), the role of microRNAs in major depression and resilience is based presumably on their influence on the expression levels of cell proteins.…”

Section: Introductionmentioning

confidence: 99%

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microRNA-15b contributes to depression-like behavior in mice by affecting synaptic protein levels and function in the nucleus accumbens

Guo

Zhao-ming

Wang

et al. 2020

Journal of Biological Chemistry

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Major depression is a prevalent affective disorder characterized by recurrent low mood. It presumably results from stress-induced deteriorations of molecular networks and synaptic functions in brain reward circuits of genetically-susceptible individuals through epigenetic processes. Epigenetic regulator microRNA-15b inhibits neuronal progenitor proliferation and is up-regulated in the medial prefrontal cortex of mice that demonstrate depression-like behavior, indicating the contribution of microRNA-15 to major depression. Using a mouse model of major depression induced by chronic unpredictable mild stress (CUMS), here we examined the effects of microRNA-15b on synapses and synaptic proteins in the nucleus accumbens of these mice. The application of a microRNA-15b antagomir into the nucleus accumbens significantly reduced the incidence of CUMS-induced depression and reversed the attenuations of excitatory synapse and syntaxin-binding protein 3 (STXBP3A)/vesicle-associated protein 1 (VAMP1) expression. In contrast, the injection of a microRNA-15b analog into the nucleus accumbens induced depression-like behavior as well as attenuated excitatory synapses and STXBP3A/VAMP1 expression similar to the down-regulation of these processes induced by the CUMS. We conclude that microRNA-15b-5p may play a critical role in chronic stress-induced depression by decreasing synaptic proteins, innervations, and activities in the nucleus accumbens. We propose that the treatment of anti-microRNA-15b-5p may convert stress-induced depression into resilience.

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Section: Discussionmentioning

confidence: 99%

Section: The Mouse Model Of Major Depression Induced By Chronic Unprementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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microRNA-15b contributes to depression-like behavior in mice by affecting synaptic protein levels and function in the nucleus accumbens

Guo

Zhao-ming

Wang

et al. 2020

Journal of Biological Chemistry

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“…Sitedirected mutation of targeted site was performed with QuikChange Lighting Site-Directed Mutagenesis Kit (Stratagene, La Jolla, CA) according to the manufacturer's instructions. Luciferase reporter detection assays were carried out as previously described [48]. Briefly, 50 ng psiCHECK2-wild-type or mutant reporter plasmids, 50 nM miRNAs mimic or miR-NC mimic were co-transfected to HEK293T cells by using Lipofectamine 2000 transfection reagent (Invitrogen, Carlsbad, CA, USA).…”

Section: Differentially Expressed Transcript Analysis and Data Analysismentioning

confidence: 99%

Molecular mechanism of reward treatment ameliorating chronic stress-induced depressive-like behavior assessed by sequencing miRNA and mRNA in medial prefrontal cortex

Song

Wang

2020

Preprint

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Background Major depressive disorder (MDD) is a disease that seriously endangers human health and mental state. Chronic stress and lack of reward may reduce the function of the brain's reward circuits, leading to major depressive disorder. The effect of reward treatment on chronic stress-induced depression-like behaviors and its molecular mechanism in the brain remain unclear.Methods Mice were divided into the groups of control, chronic unpredictable mild stress (CUMS), and CUMS-companion. Mice of CUMS group was performed by CUMS for 4 weeks, and CUMS-companion group was treated by CUMS accompanied with companion. The tests of sucrose preference, Y-maze, and forced swimming were conducted to assess depression-like behaviors or resilience. High-throughput sequencing was used to analyze mRNA and miRNA profiles in the medial prefrontal cortex harvested from control, CUMS-MDD (mice with depression-like behaviors in CUMS group), Reward-MDD (mice with depression-like behaviors in CUMS-companion group), CUMS-resilience (resilient mice in CUMS group), Reward-resilience (resilient mice in CUMS-companion group) mice.Results The results provided evidence that accompanying with companion ameliorated CUMS-induced depression-like behaviors in mice. 45 differentially expressed genes (DEGs) are associated with depression-like behaviors, 8 DEGs are associated with resilience and 59 DEGs are associated with nature reward (companion) were identified. Furthermore, 196 differentially expressed miRNAs were found to be associated with companion. Based on the differentially expressed miRNAs and DEGs data, miRNA-mRNA network was established to be associated with companion.Conclusion Taken together, our data here provided a method to ameliorate depression-like behaviors, and numerous potential drug targets for the prevention or treatment of depression.

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“…Evidence indicates that several hormones and neurotransmitter systems(such as the norepinephrine system, the GABAergic system, the serotonin system, the endocannabinoid system, the glucocorticoid system, etc.) were modulated in the amygdala during or after stress stimuli [24][25][26][27][28][29][30][31][32]. Changes in the hormone and neurotransmitter systems further contribute to the amygdala's plasticity at the cellular and neural circuits levels [33,34].…”

Section: Introductionmentioning

confidence: 99%

mRNA and microRNA profiles in the amygdala are relevant to Susceptible and Resilient mice induced by psychological stress

Sun¹,

Lu²,

Yang³

et al. 2020

Preprint

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Background Severe or prolonged stress increases the risk to develop psychopathologies. An individual's perception of stress exposure varies greatly, as do its consequences. Numerous individuals demonstrate resilience to psychological stress. The mRNA and microRNA profiles of stress susceptibility and resilience induced by psychological stress in the amygdala remain to be elucidated. Methods Psychological stress to an observer was given by witnessing the attacks of the aggressor on the similar. After five days of psychological stress, the degree of fear memory and anxiety of mice were measured by social interaction test and elevated plus-maze (EPM). mRNA and microRNA profiles were quantified by high-throughput sequencing in amygdala tissues harvested from Control, Susceptible and Resilient mice. Results In the amygdala from Susceptible mice versus Resilient mice, the upregulation of Peptide, Thyrotropin-releasing hormone, and ECM receptor, Glutamatergic synapse, Cytokine-cytokine receptor interaction, Long-term depression, PI3K-Akt, Oxytocin, GnRH, HIF-1, Estrogen, Calcium signaling pathways may be related to psychological stress-induced susceptibility, and the downregulation may be related to resilience. The downregulation of Adrenergic synapse, Adherens junction, Wnt, Sphingolipid, B cell receptor, cAMP, Rap1, Toll-like receptor signaling pathways may be related to psychological stress-induced susceptibility, and the upregulation may be related to resilience. Results by sequencing mRNA and microRNA profiles are consistent, in which some of them are validated by qRT-PCR and dual-luciferase reporter assay. Conclusion Susceptible and Resilient induced by psychological stresses are caused by the imbalanced regulation of different synapses and signaling pathways in the amygdala.

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microRNA and mRNA profiles in the amygdala are associated with stress-induced depression and resilience in juvenile mice

Cited by 32 publications

References 93 publications

microRNA-15b contributes to depression-like behavior in mice by affecting synaptic protein levels and function in the nucleus accumbens

microRNA-15b contributes to depression-like behavior in mice by affecting synaptic protein levels and function in the nucleus accumbens

Molecular mechanism of reward treatment ameliorating chronic stress-induced depressive-like behavior assessed by sequencing miRNA and mRNA in medial prefrontal cortex

mRNA and microRNA profiles in the amygdala are relevant to Susceptible and Resilient mice induced by psychological stress

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