miR-155 Is Essential for Inflammation-Induced Hippocampal Neurogenic Dysfunction

Woodbury, Maya E.; Freilich, Robert W.; Cheng, Christopher J.; Asai, Hirohide; Ikezu, Seiko; Boucher, Jonathan; Slack, Frank J.; Ikezu, Tsuneya

doi:10.1523/jneurosci.4790-14.2015

Cited by 84 publications

(56 citation statements)

References 56 publications

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“…25,26,27,28,29,30 Additionally, miR-155 is a well-known immunomodulatory miRNA that can be induced by lipopolysaccharide (LPS) and control inflammatory processes in multiple cells and organs. 31,32,33,34 However, the role of miR-155 in sepsis-induced myocardial dysfunction remains largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of miR-155 Protects Against LPS-induced Cardiac Dysfunction and Apoptosis in Mice

Wang

Bei

Huang

et al. 2016

Molecular Therapy - Nucleic Acids

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Sepsis-induced myocardial dysfunction represents a major cause of death in intensive care units. Dysregulated microRNAs (miR)-155 has been implicated in multiple cardiovascular diseases and miR-155 can be induced by lipopolysaccharide (LPS). However, the role of miR-155 in LPS-induced cardiac dysfunction is unclear. Septic cardiac dysfunction in mice was induced by intraperitoneal injection of LPS (5 mg/kg) and miR-155 was found to be significantly increased in heart challenged with LPS. Pharmacological inhibition of miR-155 using antagomiR improved cardiac function and suppressed cardiac apoptosis induced by LPS in mice as determined by echocardiography, terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) assay, and Western blot for Bax and Bcl-2, while overexpression of miR-155 using agomiR had inverse effects. Pea15a was identified as a target gene of miR-155, mediating its effects in controlling apoptosis of cardiomyocytes as evidenced by luciferase reporter assays, quantitative real time-polymerase chain reaction, Western blot, and TUNEL staining. Noteworthy, miR-155 was also found to be upregulated in the plasma of patients with septic cardiac dysfunction compared to sepsis patients without cardiac dysfunction, indicating a potential clinical relevance of miR-155. The receiver-operator characteristic curve indicated that plasma miR-155 might be a biomarker for sepsis patients developing cardiac dysfunction. Therefore, inhibition of miR-155 represents a novel therapy for septic myocardial dysfunction.

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Section: Introductionmentioning

confidence: 99%

Inhibition of miR-155 Protects Against LPS-induced Cardiac Dysfunction and Apoptosis in Mice

Wang

Bei

Huang

et al. 2016

Molecular Therapy - Nucleic Acids

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“…Woodbury et al . reported that miR-155 is the most highly elevated miRNA in primary microglia stimulated with lipopolysaccharide (LPS), which is a driver of acute inflammation3. Since miR-155 and its target genes are highly conserved across species, we hypothesized that miR-155 could be involved in stem cell maintenance and regulation of differentiation.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, mice carrying a null mutation of miR-155 display defective immune responses because of alterations in cytokine expression5152. In addition, it has been reported that miR-155 induces irregular differentiation in neuroprogenitor cells in mice3. However, it remains to be elucidated how miR-155 regulates stem cell fate.…”

Section: Discussionmentioning

confidence: 99%

“…Severe chronic neuronal inflammation can lead to irreversible neuronal damage and loss of cell populations responsible for essential sensory, motor and cognitive functions. Neural cells in the hippocampus, especially neural stem cells (NSCs), are vulnerable to inflammatory stress3. Exposure to inflammatory signals suppresses self-renewal of NSCs in the adult brain456.…”

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confidence: 99%

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Inflammation-induced miRNA-155 inhibits self-renewal of neural stem cells via suppression of CCAAT/enhancer binding protein β (C/EBPβ) expression

Obora

Onodera

Takehara

et al. 2017

Sci Rep

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Intracerebral inflammation resulting from injury or disease is implicated in disruption of neural regeneration and may lead to irreversible neuronal dysfunction. Analysis of inflammation-related microRNA profiles in various tissues, including the brain, has identified miR-155 among the most prominent miRNAs linked to inflammation. Here, we hypothesize that miR-155 mediates inflammation-induced suppression of neural stem cell (NSC) self-renewal. Using primary mouse NSCs and human NSCs derived from induced pluripotent stem (iPS) cells, we demonstrate that three important genes involved in NSC self-renewal (Msi1, Hes1 and Bmi1) are suppressed by miR-155. We also demonstrate that suppression of self-renewal genes is mediated by the common transcription factor C/EBPβ, which is a direct target of miR-155. Our study describes an axis linking inflammation and miR-155 to expression of genes related to NSC self-renewal, suggesting that regulation of miR-155 may hold potential as a novel therapeutic strategy for treating neuroinflammatory diseases.

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“…In fact, female neuroblasts are more prone to self-synthesized GABA to further enhance neurogenesis as compared to male neuroblasts (Yuan et al, 2010). Since neurotransmitters, neuromodulators, microRNAs, and cytokines all have been implicated in the modulation of dentate neurogenesis (Aimone et al, 2014; Woodbury et al, 2015), further study needs to be done to understand the critical molecular substrates and the underlying mechanisms for causing such sex differences in naïve and stress condition.…”

Section: Discussionmentioning

confidence: 99%

Sex Differences in Stress and Group Housing Effects on the Number of Newly Proliferated Cells and Neuroblasts in Middle-Aged Dentate Gyrus

Tzeng

Wang

et al. 2017

Front. Behav. Neurosci.

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Sex differences in stress and coping responses have been frequently documented in aged people, while whether such differences in aged people may appear at the middle age are unknown. This study was undertaken to study the impact of acute stress and social interaction on early neurogenesis in the dentate gyrus (DG) and hippocampus-related memory in two sexes of middle-aged mice. The number of newly proliferated cells, neuroblasts in DG, the object recognition and location memory in 9-month-old male and female C57BL/6N mice were assessed under baseline conditions as well as following an acute stressor regimen and group housing. Three conspecific companions, serving as “the housing group,” were used to model the social interaction throughout the stressor regimen. Males had lower numbers of newly proliferated cells and neuroblasts under baseline conditions as compared to females. The stressor regimen caused rapid decreases in the number of newly proliferated cells and neuroblasts in female DG but no obvious changes were observed in male DG. Group housing, regardless of companions' age, prevented the stress-induced decreases in the number of newly proliferated cells and neuroblasts in female DG. In contrast, the presence of young or age-matched companions potentiated the stress effect in males by decreasing the number of newly proliferated cells and neuroblasts. Finally, neither the stressor regimen nor group housing affected mouse performances in the object recognition and location memory in either sex. These findings, taken together, provide evidence to support a notion that middle-aged females appear to demonstrate more stress susceptibility on early neurogenesis in DG as compared to middle-aged males, although the hippocampus-related memory performances are comparable and not affected by stress in these males and females. Experiencing stress, middle-aged females are more prone to benefit from social interaction as compared to middle-aged males in this regard. We suggest, accordingly, that involving social interaction may afford a therapeutic advance in preventing stress-produced decreases in early neurogenesis in middle-aged females' DG.

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miR-155 Is Essential for Inflammation-Induced Hippocampal Neurogenic Dysfunction

Abstract: Peripheral and CNS inflammation leads to aberrations in developmental and

Cited by 84 publications

References 56 publications

Inhibition of miR-155 Protects Against LPS-induced Cardiac Dysfunction and Apoptosis in Mice

Inhibition of miR-155 Protects Against LPS-induced Cardiac Dysfunction and Apoptosis in Mice

Inflammation-induced miRNA-155 inhibits self-renewal of neural stem cells via suppression of CCAAT/enhancer binding protein β (C/EBPβ) expression

Sex Differences in Stress and Group Housing Effects on the Number of Newly Proliferated Cells and Neuroblasts in Middle-Aged Dentate Gyrus

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