Microarray Profiling Reveals Distinct Circulating miRNAs in Aged Male and Female Mice Subjected to Post-stroke Social Isolation

Banerjee, Anik; Chokkalla, Anil K; Shi, Julia J.; Lee, Jun-Young; Venna, Venugopal Reddy; Vemuganti, Raghu; McCullough, Louise D.

doi:10.1007/s12017-020-08622-2

Cited by 11 publications

(8 citation statements)

References 45 publications

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“…Specifically, altered brain expression of miR‐669c was noted in transgenic mouse models of Huntington's disease (Lee et al., 2011) and Alzheimer's disease (Ding et al., 2012). Expression of this miRNA has also been associated with behavioral resilience to chronic stress (resistance to development of depression‐like behavior following a chronic stress regimen) (Si et al., 2018), expression of social isolation stress in a poststroke mouse model (Banerjee et al., 2021), and social defeat fear memory in C57 mice (Sun et al., 2019).…”

Section: Resultsmentioning

confidence: 99%

Chronic nicotine exposure alters sperm small RNA content in C57BL/6J mouse model

Zeid

Gould

2023

Developmental Psychobiology

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Multigenerational inheritance is a nongenomic form of heritability characterized by altered phenotypes in the first generation born from the exposed parent. Multigenerational factors may account for inconsistencies and gaps in heritable nicotine addiction vulnerability. Our lab previously found that F1 offspring of male C57BL/6J mice chronically exposed to nicotine exhibited altered hippocampus functioning and related learning, nicotine-seeking, nicotine metabolism, and basal stress hormones. In an effort to identify germline mechanisms underlying these multigenerational phenotypes, the current study sequenced small RNA extracted from sperm of males chronically administered nicotine using our previously established exposure model. We identified 16 miRNAs whose expression in sperm was dysregulated by nicotine exposure. A literature review of previous research on these transcripts suggested an enrichment for regulation of psychological stress and learning. mRNAs predicted to be regulated by differentially expressed sperm small RNAs were further analyzed using exploratory enrichment analysis, which suggested potential modulation of pathways related to learning, estrogen signaling, and hepatic disease, among other findings. Overall, our findings point to links between nicotine-exposed F0 sperm miRNA and altered F1 phenotypes in this multigenerational inheritance model, particularly F1 memory, stress, and nicotine metabolism. These findings provide a valuable foundation for future functional validation of these hypotheses and characterization of mechanisms underlying male-line multigenerational inheritance.

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Section: Resultsmentioning

confidence: 99%

Chronic nicotine exposure alters sperm small RNA content in C57BL/6J mouse model

Zeid

Gould

2023

Developmental Psychobiology

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“… 31 On the other hand, miR-34b-5p may be a biomarker for poststroke social isolation of aged mice. 32 MiR-34c-5p promoted ultraviolet irradiation-induced senescence of epidermal fibroblasts. 33 MiR-34c-5p inhibits the progression of leukemia by inducing the senescence of myeloid leukemia stem cells.…”

Section: Discussionmentioning

confidence: 94%

Changes in Small Noncoding RNA Expression during Chondrocyte Senescence

et al. 2022

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Objective Osteoarthritis (OA) is characterized by the chronic and progressive deterioration of articular cartilage. Chondrocyte senescence could lead to a shift in the balance between extracellular matrix (ECM) component synthesis and degradation. Small noncoding RNAs (sncRNAs), including microRNAs (miRNAs), P-element-induced wimpy testis-(PIWI-) interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), small nuclear RNAs (snRNAs), and repeat-associated siRNAs (rasiRNAs), are a class of important epigenetic molecules. We aimed to gain insights into the changes and roles of sncRNA in chondrocyte senescence. Design Healthy mouse postnatal chondrocytes were isolated, and a replicative aging model was constructed. We used small RNA sequencing (small RNA-seq) to generate extensive small RNA data. We identified differentially expressed sncRNAs and performed tissue-specific analysis using real-time quantitative polymerase chain reaction (qRT-PCR). β-galactosidase staining was used to detect chondrocyte senescence. The results showed that the expression profiles of sncRNA in passage 5 chondrocytes were significantly different from those in passage 0 chondrocytes. The expression of sncRNA was tissue specific. We found that 40 miRNAs were upregulated and 70 miRNAs were downregulated during chondrocyte senescence, and that miR-132-5p expression inhibition prevented chondrocyte senescence. We found that 8 piRNAs were upregulated and 17 piRNAs were downregulated during chondrocyte senescence, and that piRNA piR_025576 overexpression delayed chondrocyte senescence. We found that 24 snoRNAs were upregulated and 28 snoRNAs were downregulated during chondrocyte senescence, and that snoRNA ENSMUSG00000087935 overexpression delayed chondrocyte senescence. We found that 5 snRNAs were upregulated and 6 snRNAs were downregulated during chondrocyte senescence, and that snRNA ENSMUSG00000064682 overexpression delayed chondrocyte senescence. We found that 1 rasiRNA was upregulated and 4 rasiRNAs were downregulated during chondrocyte senescence. Conclusions These findings might provide novel insights into OA pathogenesis and contribute to the development of candidates for targeted therapeutics in OA.

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“…Specifically, altered brain expression of miR-669c was noted in transgenic mouse models of Huntington’s disease [69] and Alzheimer’s disease [70]. Expression of this miRNA has also been associated with behavioral resilience to chronic stress [71], social isolation stress in a post-stroke mouse model [72], and social defeat fear memory in C57 mice [73]…”

Section: Resultsmentioning

confidence: 99%

“…Similarly, Buck and colleagues [3] noted reduced serum corticosterone in female offspring maternally exposed to nicotine. Two of the top four differentially expressed sperm miRNAs, miR-122-5p and miR-375-3p, have been linked to corticotropic signaling [43], and miR-669c-5p was associated with behavioral stress in multiple mouse models [71][72][73]. Interestingly, one study using a sperm RNA microinjection technique identified miR-375-5p (as well our 15 th differentially expressed miRNA, miR-672-5p) as among the transcripts mediating multigenerational inheritance in a paternal stress exposure model.…”

Section: Literature Review Of Differentially Expressed Sperm Mirnasmentioning

confidence: 99%

Chronic nicotine exposure alters sperm small RNA content in a C57BL/6J mouse model: Implications for multigenerational inheritance

Zeid¹,

Gould²

2022

Preprint

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Multigenerational inheritance is a non-genomic form of heritability characterized by altered phenotypes in the first generation born from the exposed parent. Multigenerational factors may account for inconsistencies and gaps in heritable nicotine addiction vulnerability. Our lab previously found that F1 offspring of male C57BL/6J mice chronically exposed to nicotine exhibited altered hippocampus functioning and related learning, nicotine-seeking, nicotine metabolism, and basal stress hormones. In an effort to identify germline mechanisms underlying these multigenerational phenotypes, the current study sequenced small RNA extracted from sperm of males chronically administered nicotine using our previously established exposure model. We identified 16 miRNAs whose expression in sperm was dysregulated by nicotine exposure. A literature review of previous research on these transcripts suggested an enrichment for regulation of psychological stress and learning. mRNAs predicted to be regulated by differentially expressed sperm small RNAs were further analyzed using biological enrichment analysis, which also supported enrichment of gene expression pathways involved in hippocampus-dependent learning. Our findings point to links between nicotine-exposed F0 sperm miRNA and altered F1 phenotypes in this multigenerational inheritance model. Specifically, differentially expressed F0 sperm miRNAs may regulate the previously observed changes in F1 learning and stress. These findings provide a valuable foundation for future functional validation of these hypotheses and characterization of mechanisms underlying male-line multigenerational inheritance.

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Microarray Profiling Reveals Distinct Circulating miRNAs in Aged Male and Female Mice Subjected to Post-stroke Social Isolation

Cited by 11 publications

References 45 publications

Chronic nicotine exposure alters sperm small RNA content in C57BL/6J mouse model

Chronic nicotine exposure alters sperm small RNA content in C57BL/6J mouse model

Changes in Small Noncoding RNA Expression during Chondrocyte Senescence

Chronic nicotine exposure alters sperm small RNA content in a C57BL/6J mouse model: Implications for multigenerational inheritance

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