MiR-497 promotes microglia activation and proinflammatory cytokines production in chronic unpredictable stress-induced depression via targeting FGF2

Zhai, Xiaoyan; Liu, Jing; Ni, Aihua; Ye, Jun

doi:10.1016/j.jchemneu.2020.101872

Cited by 14 publications

(7 citation statements)

References 34 publications

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“…Although a research has shown that knockdown of miR-497 could improve rat depression [ 19 ], the detailed action of miR-497-5p in depression remains to be elucidated. Subsequently, viral vectors containing miR-497-5p inhibitor were injected into the hippocampal region of CUMS-induced mice.…”

Section: Resultsmentioning

confidence: 99%

Long Noncoding RNA LINC00473 Ameliorates Depression-Like Behaviors in Female Mice by Acting as a Molecular Sponge to Regulate miR-497-5p/BDNF Axis

Zhao

Sun

2022

Computational and Mathematical Methods in Medicine

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Background. Depression was a common life-threatening psychiatric disorder and occurs more frequently in women than in men. Long noncoding RNAs (lncRNAs), such as LINC00473, had been reported to be involved in the progression of depression. Methods. Chronic unpredictable moderate stress in mice (CUMS) was applied to construct a depression model. Subsequently, RT-qPCR was applied to check the level of LINC00473 and microRNA-497-5p (miR-497-5p) in the hippocampal region of the mice induced by CUMS. CUMS mice were injected with lentiviral vectors of LINC00473 (LV-LINC00473), miR-497-5p inhibitor, short hairpin- (sh-) brain-derived neurotrophic factor (sh-BDNF), or miR-497-5p mimic to evaluate depressive behaviors, including sucrose preference test, forced swim test, elevated plus maze, and tail suspension test. Moreover, the production of hypothalamic neurotransmitters was assessed with the usage of ELISA kits. Dual-luciferase reporter assay, RNA pull-down, and RIP analysis were performed to measure the relationship between miR-497-5p and LINC00473 or BDNF. Further, western blot was employed to determine the protein level of BDNF. Results. We discovered that LINC00473 level was downregulated in the female mice with depression, but not in male mice. Besides, the depressive behaviors induced by CUMS in mice, including the decrease of sucrose preference and time in open arm, as well as the increase of immobility time and swimming resting time were all ameliorated by LINC00473 overexpression. Moreover, the concentration of neurotransmitters was decreased in CUMS-induced mouse hypothalamus, which was blocked by LV-LINC00473 lentiviral vector administration. Mechanistically, LINC00473 directly targeted miR-497-5p. Absence of miR-497-5p revealed the antidepression effects on CUMS-induced mice, and miR-497-5p upregulation could counter the antidepressive impacts of LINC00473 upregulation on CUMS-induced mice. Furthermore, LINC00473 could target miR-497-5p to modulate BDNF level. Knockdown of BDNF could abrogate the improving influences of miR-497-5p suppression on CUMS-induced depression. Conclusions. LINC00473 ameliorated CUMS-caused depression by encouraging BDNF expression via binding to miR-497-5p, which might provide a potential therapeutic target for depression in females.

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Section: Resultsmentioning

confidence: 99%

Long Noncoding RNA LINC00473 Ameliorates Depression-Like Behaviors in Female Mice by Acting as a Molecular Sponge to Regulate miR-497-5p/BDNF Axis

Zhao

Sun

2022

Computational and Mathematical Methods in Medicine

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“…FGF2 is a direct target of miR‐497 in microglia and overexpression of FGF2 inhibited miR‐497‐induced proinflammatory cytokines. These studies suggest that miR‐497 enhanced hippocampal microglial activation in CUS‐induced depression in part by suppressing production of FGF2 (Zhai et al, 2020).…”

Section: Fgf Signaling In the Brain And Sensory Organsmentioning

confidence: 99%

New developments in the biology of fibroblast growth factors

Ornitz

Itoh

2022

WIREs Mechanisms of Disease

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The fibroblast growth factor (FGF) family is composed of 18 secreted signaling proteins consisting of canonical FGFs and endocrine FGFs that activate four receptor tyrosine kinases (FGFRs 1-4) and four intracellular proteins (intracellular FGFs or iFGFs) that primarily function to regulate the activity of voltagegated sodium channels and other molecules. The canonical FGFs, endocrine FGFs, and iFGFs have been reviewed extensively by us and others. In this review, we briefly summarize past reviews and then focus on new developments in the FGF field since our last review in 2015. Some of the highlights in the past 6 years include the use of optogenetic tools, viral vectors, and inducible transgenes to experimentally modulate FGF signaling, the clinical use of small molecule FGFR inhibitors, an expanded understanding of endocrine FGF signaling, functions for FGF signaling in stem cell pluripotency and differentiation, roles for FGF signaling in tissue homeostasis and regeneration, a continuing elaboration of mechanisms of FGF signaling in development, and an expanding appreciation of roles for FGF signaling in neuropsychiatric diseases.

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“…In particular, RT-PCR validation confirmed that miR-497 in SCZ had significantly higher expression when compared to controls [41] . Zhai XY et al [42] revealed through luciferase activity assay that fibroblast growth factor 2 (FGF2) are a direct target of miR-497 and are regulated by miR-497 in microglia. The authors also demonstrated that the knockdown expression of miR-497 inhibited the activation of microglia and production of proinflammatory cytokines including IL- Accepted manuscript: Authors' Copy and TNF-α in CUS-induced rats while an overexpression of FGF2 inhibited miR-497induced proinflammatory cytokines and iNOS expression.…”

Section: Introductionmentioning

confidence: 99%

Exosomes in schizophrenia: Pathophysiological mechanisms, biomarkers, and therapeutic targets

2022

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While schizophrenia (SCZ) is a devastating psychiatric disorder that detrimentally affects a significant portion of the worldwide population, its diagnosis is traditionally based on a relatively subjective assessment of current symptoms and medical history, devoid of an objective diagnostic modality. Antipsychotic medications are commonly used in the treatment of SCZ; however, some patients have low remission rates or forsake treatment due to the associated multiple side effects, resulting in recurrent

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MiR-497 promotes microglia activation and proinflammatory cytokines production in chronic unpredictable stress-induced depression via targeting FGF2

Cited by 14 publications

References 34 publications

Long Noncoding RNA LINC00473 Ameliorates Depression-Like Behaviors in Female Mice by Acting as a Molecular Sponge to Regulate miR-497-5p/BDNF Axis

Long Noncoding RNA LINC00473 Ameliorates Depression-Like Behaviors in Female Mice by Acting as a Molecular Sponge to Regulate miR-497-5p/BDNF Axis

New developments in the biology of fibroblast growth factors

Exosomes in schizophrenia: Pathophysiological mechanisms, biomarkers, and therapeutic targets

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