TY  - JOUR
AU  - Kaurani, Lalit
AU  - Islam, Rezaul
AU  - Heilbronner, Urs
AU  - Krüger, Dennis M
AU  - Zhou, Jiayin
AU  - Methi, Aditi
AU  - Strauss, Judith
AU  - Pradhan, Ranjit
AU  - Schröder, Sophie
AU  - Burkhardt, Susanne
AU  - Schuetz, Anna-Lena
AU  - Pena, Tonatiuh
AU  - Erlebach, Lena
AU  - Bühler, Anika
AU  - Budde, Monika
AU  - Senner, Fanny
AU  - Kohshour, Mojtaba Oraki
AU  - Schulte, Eva C
AU  - Schmauß, Max
AU  - Reininghaus, Eva Z
AU  - Juckel, Georg
AU  - Kronenberg-Versteeg, Deborah
AU  - Delalle, Ivana
AU  - Odoardi, Francesca
AU  - Flügel, Alexander
AU  - Schulze, Thomas G
AU  - Falkai, Peter
AU  - Sananbenesi, Farahnaz
AU  - Fischer, Andre
TI  - Regulation of Zbp1 by miR-99b-5p in microglia controls the development of schizophrenia-like symptoms in mice.
JO  - The EMBO journal
VL  - 43
IS  - 8
SN  - 0261-4189
CY  - Hoboken, NJ [u.a.]
PB  - Wiley
M1  - DZNE-2024-00487
SP  - 1420 - 1444
PY  - 2024
AB  - 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.
KW  - RNA-Binding Proteins: metabolism
KW  - Humans
KW  - Animals
KW  - Mice
KW  - Microglia: metabolism
KW  - Schizophrenia: genetics
KW  - MicroRNAs: metabolism
KW  - RNA-Binding Proteins
KW  - Mirn99 microRNA, mouse (NLM Chemicals)
KW  - Microglia (Other)
KW  - Schizophrenia (Other)
KW  - Zbp1 (Other)
KW  - miR-99b (Other)
KW  - microRNA (Other)
KW  - MicroRNAs (NLM Chemicals)
KW  - Zbp1 protein, mouse (NLM Chemicals)
KW  - RNA-Binding Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:38528182
C2  - pmc:PMC11021462
DO  - DOI:10.1038/s44318-024-00067-8
UR  - https://pub.dzne.de/record/269188
ER  -