miRNA

Astrocyte reprogramming / activation and brain homeostasis

Astrocytes are multifunctional glial cells, implicated in neurogenesis and synaptogenesis, supporting and fine-tuning neuronal activity and maintaining brain homeostasis by controlling blood-brain barrier permeability. During the last years a number of studies have shown that astrocytes can also be converted into neurons if they force-express neurogenic transcription factors or miRNAs. Direct astrocytic reprogramming to induced-neurons (iNs) is a powerful approach for manipulating cell fate, as it takes advantage of the intrinsic neural stem cell (NSC) potential of brain resident reactive astrocytes. To this end, astrocytic cell fate conversion to iNs has been well-established in vitro and in vivo using combinations of transcription factors (TFs) or chemical cocktails. Challenging the expression of lineage-specific TFs is accompanied by changes in the expression of miRNAs, that post-transcriptionally modulate high numbers of neurogenesis-promoting factors and have therefore been introduced, supplementary or alternatively to TFs, to instruct direct neuronal reprogramming. The neurogenic miRNA miR-124 has been employed in direct reprogramming protocols supplementary to neurogenic TFs and other miRNAs to enhance direct neurogenic conversion by suppressing multiple non-neuronal targets. In our group we aimed to investigate whether miR-124 is sufficient to drive direct reprogramming of astrocytes to induced-neurons (iNs) on its own both in vitro and in vivo and elucidate its independent mechanism of reprogramming action. Our in vitro data indicate that miR-124 is a potent driver of the reprogramming switch of astrocytes towards an immature neuronal fate. Elucidation of the molecular pathways being triggered by miR-124 by RNA-seq analysis revealed that miR-124 is sufficient to instruct reprogramming of cortical astrocytes to immature induced-neurons (iNs) in vitro by down-regulating genes with important regulatory roles in astrocytic function. Among these, the RNA binding protein Zfp36l1, implicated in ARE-mediated mRNA decay, was found to be a direct target of miR-124, that be its turn targets neuronal-specific proteins participating in cortical development, which get de-repressed in miR-124-iNs. Furthermore, miR-124 is potent to guide direct neuronal reprogramming of reactive astrocytes to iNs of cortical identity following cortical trauma, a novel finding confirming its robust reprogramming action within the cortical microenvironment under neuroinflammatory conditions. In parallel to their reprogramming properties, astrocytes also participate in the maintenance of blood-brain barrier integrity, which ensures the physiological functioning of the central nervous system and gets affected contributing to the pathology of several neurodegenerative diseases. To study in real time the dynamic physical interactions of astrocytes with brain vasculature under homeostatic and pathological conditions, we performed 2-photon brain intravital imaging in a mouse model of systemic neuroinflammation, known to trigger astrogliosis and microgliosis and to evoke changes in astrocytic contact with brain vasculature. Our in vivo findings indicate that following neuroinflammation the endfeet of activated perivascular astrocytes lose their close proximity and physiological cross-talk with vasculature, however this event is at compensated by the cross-talk of astrocytes with activated microglia, safeguarding blood vessel coverage and maintenance of blood-brain integrity.

miRNA dysregulation in embryo results in autism spectrum disorder

Alogliptin Attenuates Lipopolysaccharide-Induced Neuroinflammation in Mice Through Modulation of TLR4/MYD88/NF-κB and miRNA-155/SOCS-1 Signaling Pathways

Consistent metabolic and miRNA signatures of childhood trauma across different body fluids in human

Contribution of c-Fos expression in the arcuate nucleus to the development of obesity in miRNA-deficient mice

Epigenetic regulation of orexin neurons by miRNAs

Ethanol-induced miRNA 137 and 501-3p modulate AMPA neurotransmission in developing hippocampal slices in vitro

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A miRNA fingerprint in Plasma-derived extracellular vesicles of hSOD1G93A transgenic swine

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ATP stimulation regulates astrocyte-derived extracellular vesicle secretion and miRNA content

Analysis of NR4A2-related miRNAs in Alzheimer's disease biological samples

FENS Forum 2024

A CNS-enriched miRNA as a biomarker for major depressive disorder

FENS Forum 2024

Differential expression of prefrontal cortex miRNAs involved in depression-related pathways

FENS Forum 2024

Evaluation of potential biomarker miRNAs and the levels of serotonin in patients with obsessive-compulsive disorder

FENS Forum 2024

Exploring synergistic miRNA therapy for Alzheimer’s: AAV-mediated delivery of miR-124 and miR-132

FENS Forum 2024

Do neurotransmitters regulate astrocyte-derived extracellular vesicle secretion and miRNA content?

FENS Forum 2024

Protective effects of intracranial stimulation on spatial memory and changes in miRNA serum levels in a sporadic rat model of Alzheimer disease: A longitudinal study

FENS Forum 2024

Synergistic, long-term effects of glutamate dehydrogenase 1 deficiency and mild stress on cognitive function and mPFC gene and miRNA expression

FENS Forum 2024

Temporal regulation of voltage-gated sodium channels by miRNAs during hippocampal development: Insights from Argonaute sequencing

FENS Forum 2024

In vitro studying of the role of miRNAs in neuronal injury and regeneration

FENS Forum 2024