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BMP4 Exerts Anti-Neurogenic Effect via Inducing Id3 during Aging.
Tingting Li1, Hongmei Liu1,2,3, Dongfang Jiang1
1State Key Laboratory of Membrane Biology, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100101, China.
Biomedicines
|May 28, 2022
Summary
Increased bone morphogenetic protein 4 (BMP4) signaling with age inhibits adult neurogenesis in the brain. This age-related decline in neurogenesis is linked to the Id3-NeuroD1 pathway in neuronal stem cells.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Adult neurogenesis, crucial for brain repair, declines with age.
- The precise role of bone morphogenetic protein (BMP) signaling in this age-related decline is not fully understood.
- Previous studies on BMP4's effect on neurogenesis have yielded controversial results.
Purpose of the Study:
- To investigate the role of BMP4 signaling in age-related neurogenesis decline in the murine subventricular zone (SVZ) and subgranular zone (SGZ).
- To elucidate the molecular mechanisms by which BMP4 influences neurogenesis and neuronal differentiation.
Main Methods:
- Analysis of BMP4 and phosphorylated-Smad1/5/8 (p-Smad1/5/8) expression in aging murine SVZ and SGZ.
- Intracerebroventricular infusion of BMP4 and noggin (BMP inhibitor) in mice.
- Assessment of Id3 and NeuroD1 expression in neuronal stem cells (NSCs).
- Evaluation of neurogenesis and differentiation following BMP4 treatment or Id3 overexpression.
Main Results:
- BMP4 and p-Smad1/5/8 expression increased significantly with age in the SVZ and SGZ.
- Id3, a downstream target of BMP4, also increased with age in NSCs from both neurogenic regions.
- BMP4 infusion upregulated Id3, suppressed NeuroD1, attenuated neurogenesis, and impaired differentiation.
- Noggin administration reversed these effects.
- BMP4 treatment or Id3 overexpression reduced NeuroD1 levels and inhibited neurogenesis.
Conclusions:
- Increased BMP4 signaling contributes to the age-related decline in adult neurogenesis in the SVZ and SGZ.
- The Id3-NeuroD1 axis is a key mediator of BMP4's inhibitory effects on neurogenesis and differentiation.
- Targeting the BMP4-Id3-NeuroD1 pathway may offer therapeutic strategies to counteract age-related neurogenesis deficits.
