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Research Topics: MicroRNAs (miRNAs) rapidly emerge as global regulators of gene expression, yet their roles in brain functioning are largely unknown. We combine advanced sequencing technologies with computational neuroscience and transgenic engineering tools to investigate miRNA functions in the healthy and diseased brain, with a focus on acetylcholine signaling and its ‘CholinomiRs’ microRNA controllers. We discovered cholinergic brain-to-body regulation of anxiety and inflammation, and found "CholinomiR" silencers of multiple genes that compete with each other on suppressing their targets. We currently introduce this dimension of complexity to CholinomiR interactions, clarify its impact on anxiety and neurodegeneration, and test CholinomiR-based intervention with diseases involving impaired ACh signaling. In human volunteers, we find single nucleotide polymorphism (SNP) interference with acetylcholinesterase (AChE)-targeting CholinomiR functioning to associate with elevated trait anxiety, blood pressure and inflammation. In experimental animal models, we study CholinomiR increases under acute stress, inflammation and ischemic stroke, whereas in Alzheimer’s brains we see massive CholinomiRs decline and accompanying modifications in alternative splicing and transcript termination that differ from those of Parkinson’s disease. Finally, we engineer "humanized" mice and neuronal stem cells carrying such primate-specific CholinomiRs for studying their contributions to higher brain functions.
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Cellular and Molecular Life Sciencesno. 1 (2024): 1-14
JOURNAL OF NEUROCHEMISTRY (2024)
MOLECULAR METABOLISM (2024)
Brain communicationsno. 2 (2024): fcae099-fcae099
bioRxiv (Cold Spring Harbor Laboratory) (2024): 101856-101856
MOVEMENT DISORDERSno. 7 (2023): 1127-1142
RNA technologiespp.1-19, (2023)
Journal of neurochemistry (2023)
Cellsno. 13 (2023): 1794-1794
Journal of neurochemistry (2023)
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