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Robust RBM3 and β-klotho expression in developing neurons in the human brain
Travis C Jackson1, Keri Janesko-Feldman2,3, Shaun W Carlson4
1Department of Molecular Pharmacology & Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Summary
RNA binding motif 3 (RBM3) and its receptor β-klotho are abundant in infant neurons, suggesting a role in early brain development and neuroprotection. This finding is crucial for future therapeutic strategies targeting neurodegenerative diseases.
Area of Science:
- Neuroscience
- Molecular Biology
- Developmental Biology
Background:
- RNA binding motif 3 (RBM3) is a neuroprotectant targeting neurodegenerative diseases and brain ischemia.
- Fibroblast growth factor 21 (FGF21) increases RBM3 in rat neurons, but its receptor, β-klotho, is scarce in adult brains.
- Previous studies showed high RBM3/β-klotho in infant human brains but lacked cell-type specificity.
Purpose of the Study:
- To investigate the cell-type-specific expression of RBM3 and β-klotho in the developing human brain.
- To determine if RBM3/β-klotho is expressed in neurons, supporting its neuroprotective role in early life.
Main Methods:
- Acquisition of human brain tissues (hippocampus, cortex, hypothalamus) from infants and adults via the NIH Neurobiobank.
- Dual labeling immunohistochemistry using cell-type markers alongside RBM3/β-klotho staining.
- Microscopic analysis to compare expression patterns across different age groups and cell types.
Main Results:
- RBM3 and β-klotho showed enriched staining in neurons of the developing human brain (infants and young children).
- Expression levels were significantly higher in immature neuronal cells compared to adult brain tissues.
- Confirmed neuronal localization of RBM3/β-klotho in the immature central nervous system.
Conclusions:
- RBM3/β-klotho is predominantly expressed in neurons during early human brain development.
- This neuronal abundance highlights a critical neuroprotective pathway active in the immature brain.
- Findings provide essential groundwork for designing future therapeutic interventions for neurological disorders.
