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Inhibiting proBDNF to mature BDNF conversion leads to ASD-like phenotypes in vivo
- Source :
- Molecular Psychiatry; 20240101, Issue: Preprints p1-13, 13p
- Publication Year :
- 2024
-
Abstract
- Autism Spectrum Disorders (ASD) comprise a range of early age-onset neurodevelopment disorders with genetic heterogeneity. Most ASD related genes are involved in synaptic function, which is regulated by mature brain-derived neurotrophic factor (mBDNF) and its precursor proBDNF in a diametrically opposite manner: proBDNF inhibits while mBDNF potentiates synapses. Here we generated a knock-in mouse line (BDNFmet/leu) in which the conversion of proBDNF to mBDNF is attenuated. Biochemical experiments revealed residual mBDNF but excessive proBDNF in the brain. Similar to other ASD mouse models, the BDNFmet/leumice showed reduced dendritic arborization, altered spines, and impaired synaptic transmission and plasticity in the hippocampus. They also exhibited ASD-like phenotypes, including stereotypical behaviors and deficits in social interaction. Moreover, the plasma proBDNF/mBDNF ratio was significantly increased in ASD patients compared to normal children in a case-control study. Thus, deficits in proBDNF to mBDNF conversion in the brain may contribute to ASD-like behaviors, and plasma proBDNF/mBDNF ratio may be a potential biomarker for ASD.
Details
- Language :
- English
- ISSN :
- 13594184 and 14765578
- Issue :
- Preprints
- Database :
- Supplemental Index
- Journal :
- Molecular Psychiatry
- Publication Type :
- Periodical
- Accession number :
- ejs66412674
- Full Text :
- https://doi.org/10.1038/s41380-024-02595-5