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Updated: Jan 12, 2026
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Radiation Treatment of Organotypic Cultures from Submandibular and Parotid Salivary Glands Models Key In Vivo Characteristics
Published on: May 17, 2019
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Zinc Modulates Neurturin-AKT Signaling to Promote Parasympathetic Innervation in Developing Submandibular Salivary
Gulsan Ara Sathi Kazi1, Hiroki Nakagawa1, Sayaka Fujihara1
1Graduate School of Science and Engineering, Yamagata University, Yamagata, Japan.
Journal of Neurochemistry
|October 31, 2025
Summary
This study reveals that zinc supplementation enhances salivary gland development and nerve growth by interacting with neurturin and activating the PI3K/AKT pathway. This finding highlights zinc
Area of Science:
- Neuroscience
- Developmental Biology
- Biochemistry
Background:
- Zinc (Zn2+) is vital for neural development, but its role in parasympathetic innervation is unclear.
- Submandibular salivary gland (SMG) development involves complex interactions influencing innervation.
- The PI3K/AKT signaling pathway is crucial for neuronal development and survival.
Purpose of the Study:
- To investigate the interplay between Zn2+ and neurturin (NRTN) in SMG development.
- To elucidate the role of the PI3K/AKT pathway in Zn2+-mediated parasympathetic innervation.
- To explore the therapeutic potential of zinc in salivary gland regeneration.
Main Methods:
- Utilized an ex vivo embryonic mouse SMG organ culture system.
- Employed a bioengineered hydrogel for sustained Zn2+ delivery.
- Investigated signaling pathways using pharmacological inhibitors and NRTN.
Main Results:
- Zinc supplementation significantly improved epithelial branching and neurite outgrowth in SMGs.
- Zn2+ activated the PI3K/AKT pathway, promoting epithelial and neuronal development.
- NRTN, an upstream activator of AKT, showed enhanced signaling with Zn2+; co-administration rescued development despite pathway inhibition.
Conclusions:
- Zn2+ and NRTN exhibit synergistic effects on SMG development and parasympathetic innervation.
- A novel crosstalk between metal ion and neurotrophin signaling pathways was identified.
- Zinc holds therapeutic promise for salivary gland dysfunction and related autonomic innervation disorders.
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