Journal Article

DZNE-2024-00487

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Regulation of Zbp1 by miR-99b-5p in microglia controls the development of schizophrenia-like symptoms in mice.

Kaurani, L. (First author)DZNE* ; Islam, R. (First author)DZNE* ; Heilbronner, U. ; Krüger, D. M.DZNE* ; Zhou, J.DZNE* ; Methi, A.DZNE* ; Strauss, J. ; Pradhan, R.DZNE* ; Schröder, S.DZNE* ; Burkhardt, S.DZNE* ; Schuetz, A.-L.DZNE* ; Pena, T.DZNE* ; Erlebach, L.DZNE* ; Bühler, A.DZNE* ; Budde, M. ; Senner, F. ; Kohshour, M. O. ; Schulte, E. C. ; Schmauß, M. ; Reininghaus, E. Z. ; Juckel, G. ; Kronenberg-Versteeg, D.DZNE* ; Delalle, I. ; Odoardi, F. ; Flügel, A. ; Schulze, T. G. ; Falkai, P. ; Sananbenesi, F.Extern* ; Fischer, A.DZNE*

2024
Wiley Hoboken, NJ [u.a.]

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Please use a persistent id in citations: doi:10.1038/s44318-024-00067-8

Abstract: Current approaches to the treatment of schizophrenia have mainly focused on the protein-coding part of the genome; in this context, the roles of microRNAs have received less attention. In the present study, we analyze the microRNAome in the blood and postmortem brains of schizophrenia patients, showing that the expression of miR-99b-5p is downregulated in both the prefrontal cortex and blood of patients. Lowering the amount of miR-99b-5p in mice leads to both schizophrenia-like phenotypes and inflammatory processes that are linked to synaptic pruning in microglia. The microglial miR-99b-5p-supressed inflammatory response requires Z-DNA binding protein 1 (Zbp1), which we identify as a novel miR-99b-5p target. Antisense oligonucleotides against Zbp1 ameliorate the pathological effects of miR-99b-5p inhibition. Our findings indicate that a novel miR-99b-5p-Zbp1 pathway in microglia might contribute to the pathogenesis of schizophrenia.

Keyword(s): RNA-Binding Proteins: metabolism (MeSH) ; Humans (MeSH) ; Animals (MeSH) ; Mice (MeSH) ; Microglia: metabolism (MeSH) ; Schizophrenia: genetics (MeSH) ; MicroRNAs: metabolism (MeSH) ; RNA-Binding Proteins (MeSH) ; Mirn99 microRNA, mouse ; Microglia ; Schizophrenia ; Zbp1 ; miR-99b ; microRNA ; MicroRNAs ; Zbp1 protein, mouse ; RNA-Binding Proteins

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Contributing Institute(s):

1. Epigenetics and Systems Medicine in Neurodegenerative Diseases (AG Fischer)
2. Glial Cell Biology (AG Kronenberg-Versteeg)
3. Cell Biology of Neurological Diseases (AG Jucker)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)
2. 351 - Brain Function (POF4-351) (POF4-351)

Appears in the scientific report 2024

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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