Inhibition of miR-141-3p Ameliorates the Negative Effects of Poststroke Social Isolation in Aged Mice

Verma, Rajkumar; Ritzel, Rodney M.; Harris, Nia; Lee, Jun-Young; Kim, Tae-Hee; Pandi, Gopal; Vemuganti, Raghu; McCullough, Louise D.

doi:10.1161/strokeaha.118.020627

Cited by 30 publications

(39 citation statements)

References 42 publications

(64 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MiR-141-3p was selected because of its relatively high abundance and was exclusively secreted under IL-1β stress. Moreover, increased expression of miR-141-3p has been reported after neuroinflammatory conditions such as stroke [15]. MiR-30d was selected from the pool of miRNAs due to its increased expression after IL-1β treatment.…”

Section: Resultsmentioning

confidence: 99%

Exosomal MicroRNAs Released by Activated Astrocytes as Potential Neuroinflammatory Biomarkers

Gayen

Bhomia

Balakathiresan

et al. 2020

IJMS

View full text Add to dashboard Cite

Neuroinflammation is a hallmark of several neurodegenerative diseases and disorders, including traumatic brain injury (TBI). Neuroinflammation results in the activation of glial cells which exacerbates the neuroinflammatory process by secretion of pro-inflammatory cytokines and results in disruption of glial transmission networks. The glial cells, including astrocytes, play a critical role in the maintenance of homeostasis in the brain. Activated astrocytes release several factors as part of the inflammatory process including cytokines, proteins, and microRNAs (miRNAs). MiRNAs are noncoding RNA molecules involved in normal physiological processes and disease pathogenesis. MiRNAs have been implicated as important cell signaling molecules, and they are potential diagnostic biomarkers and therapeutic targets for various diseases, including neurological disorders. Exosomal miRNAs released by astrocytic response to neuroinflammation is not yet studied. In this study, primary human astrocytes were activated by IL-1β stimulation and we examined astrocytic exosomal miRNA cargo released in a neuroinflammatory stress model. Results indicate that acute neuroinflammation and oxidative stress induced by IL-1β generates the release of a specific subset of miRNAs via exosomes, which may have a potential role in regulating the inflammatory response. Additionally, these miRNAs may serve as potential biomarkers of neuroinflammation associated with neurological disorders and injuries.

show abstract

Section: Resultsmentioning

confidence: 99%

Exosomal MicroRNAs Released by Activated Astrocytes as Potential Neuroinflammatory Biomarkers

Gayen

Bhomia

Balakathiresan

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…Some studies reported an association between social isolation and consequent psychological stress and miRNA dysregulation. For instance, miR-141-3p expression progressively increases in a time-dependent manner in mouse models of post-stroke social isolation [ 88 ], and members of the miR-29 family increased their expression during the healing process of oral palatal mucosal wounds [ 89 ]. Moreover, decreasing plasmatic let-7b-5p correlated strongly with cognitive impairment in the presence of severe alcohol use disorder [ 90 ] and it was also related to high stress conditions [ 91 ].…”

Section: Discussionmentioning

confidence: 99%

Potential Associations Among Alteration of Salivary miRNAs, Saliva Microbiome Structure, and Cognitive Impairments in Autistic Children

Ragusa

Santagati

Mirabella

et al. 2020

IJMS

View full text Add to dashboard Cite

Recent evidence has demonstrated that salivary molecules, as well as bacterial populations, can be perturbed by several pathological conditions, including neuro-psychiatric diseases. This relationship between brain functionality and saliva composition could be exploited to unveil new pathological mechanisms of elusive diseases, such as Autistic Spectrum Disorder (ASD). We performed a combined approach of miRNA expression profiling by NanoString technology, followed by validation experiments in qPCR, and 16S rRNA microbiome analysis on saliva from 53 ASD and 27 neurologically unaffected control (NUC) children. MiR-29a-3p and miR-141-3p were upregulated, while miR-16-5p, let-7b-5p, and miR-451a were downregulated in ASD compared to NUCs. Microbiome analysis on the same subjects revealed that Rothia, Filifactor, Actinobacillus, Weeksellaceae, Ralstonia, Pasteurellaceae, and Aggregatibacter increased their abundance in ASD patients, while Tannerella, Moryella and TM7-3 decreased. Variations of both miRNAs and microbes were statistically associated to different neuropsychological scores related to anomalies in social interaction and communication. Among miRNA/bacteria associations, the most relevant was the negative correlation between salivary miR-141-3p expression and Tannerella abundance. MiRNA and microbiome dysregulations found in the saliva of ASD children are potentially associated with cognitive impairments of the subjects. Furthermore, a potential cross-talking between circulating miRNAs and resident bacteria could occur in saliva of ASD.

show abstract

“…CCK transcription can also be modulated by other stressors such as maternal separation (Weidner et al, 2019). In rodents, chronic social isolation stress can trigger widespread changes in the transcription of protein-coding and non-coding genes (Karelina et al, 2009;Wallace et al, 2009;Liu et al, 2012a;Jin et al, 2016;Kumari et al, 2016;Verma et al, 2016Verma et al, , 2018Zelikowsky et al, 2018;Mavrikaki et al, 2019;Chang et al, 2020). In adult mice, social isolation for 8 weeks induces transcriptional changes in the myelin genes Mbop and Mobp in oligodendrocytes of the prefrontal cortex (PFC) (Liu et al, 2012a).…”

Section: Social Isolation Induces Changes In Gene Expressionmentioning

confidence: 99%

“…Social isolation in rodents can also affect the expression of non-coding RNAs like miRNAs (Kumari et al, 2016;Verma et al, 2018;Mavrikaki et al, 2019;Antony et al, 2020, p. 181;Chang et al, 2020). Prolonged isolation of postnatal rats resulted in differential miRNAs expression in the anterodorsal bed nucleus of the stria terminalis (adBNS), a region involved in anxiety responses (Mavrikaki et al, 2019).…”

Section: Social Isolation Induces Changes In Gene Expressionmentioning

confidence: 99%

“…Interestingly, the level of miR-29a was also altered in other tissues such as the oral cavity (Yang et al, 2013), suggesting systemic responses to social isolation. miR-181c expression was also downregulated in the brain of isolated mice after stroke (Verma et al, 2018;Antony et al, 2020) while the levels of miR-181a are affected in blood of adult humans with a history of childhood trauma (Mavrikaki et al, 2019), suggesting that miR-181 family members could be a common target of stress responses in mammals.…”

Section: Social Isolation Induces Changes In Gene Expressionmentioning

confidence: 99%

See 1 more Smart Citation

Long-Term Impact of Social Isolation and Molecular Underpinnings

Arzate-Mejía

Lottenbach²,

Schindler³

et al. 2020

Front. Genet.

View full text Add to dashboard Cite

Prolonged periods of social isolation can have detrimental effects on the physiology and behavior of exposed individuals in humans and animal models. This involves complex molecular mechanisms across tissues in the body which remain partly identified. This review discusses the biology of social isolation and describes the acute and lasting effects of prolonged periods of social isolation with a focus on the molecular events leading to behavioral alterations. We highlight the role of epigenetic mechanisms and non-coding RNA in the control of gene expression as a response to social isolation, and the consequences for behavior. Considering the use of strict quarantine during epidemics, like currently with COVID-19, we provide a cautionary tale on the indiscriminate implementation of such form of social isolation and its potential damaging and lasting effects in mental health.

show abstract

Inhibition of miR-141-3p Ameliorates the Negative Effects of Poststroke Social Isolation in Aged Mice

Abstract: miR-141-3p is increased with poststroke isolation. Inhibition of miR-141-3p improved mortality, neurological deficits, and decreased infarct volumes. Importantly, these therapeutic effects occurred in aged animals, the population most at risk for stroke and poststroke isolation.

Cited by 30 publications

References 42 publications

Exosomal MicroRNAs Released by Activated Astrocytes as Potential Neuroinflammatory Biomarkers

Exosomal MicroRNAs Released by Activated Astrocytes as Potential Neuroinflammatory Biomarkers

Potential Associations Among Alteration of Salivary miRNAs, Saliva Microbiome Structure, and Cognitive Impairments in Autistic Children

Long-Term Impact of Social Isolation and Molecular Underpinnings

Contact Info

Product

Resources

About