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Neurotoxic stimulation alters prosaposin levels in the salivary systems of rats

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Abstract

Prosaposin (PSAP), a potent neurotrophic factor, is found in neuronal and non-neuronal tissues and various biological fluids. Neuropathological conditions often alter PSAP production in neural tissues. However, little is known about its alterations in non-neural tissues, particularly in the salivary glands, which are natural reservoirs of various neurotrophic factors. In this study, we explored whether neurotoxic stimulation by kainic acid (KA), a glutamate analog, altered PSAP levels in the salivary system of rats. The results revealed that KA injection did not alter total saliva production. However, KA-induced neurotoxic stimulation significantly increased the PSAP level in the secreted saliva but decreased it in the serum. In addition, KA-induced elevated immunoreactivities of PSAP and its receptors have been observed in the granular convoluted tubule (GCT) cells of the submandibular gland (SMG), a major salivary secretory organ. Indeed, a large number of PSAP-expressing immunogold particles were observed in the secretory granules of the SMG. Furthermore, KA-induced overexpression of PSAP was co-localized with secretogranin in secretory acini (mostly in GCT cells) and the ductal system of the SMG, suggesting the release of excess PSAP from the salivary glands into the oral cavity. In conclusion, the salivary system produces more PSAP during neurotoxic conditions, which may play a protective role in maintaining the secretory function of the salivary glands and may work in distant organs.

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The datasets used and/or analyzed during the study are available from the corresponding author upon reasonable request.

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Acknowledgements

We would like to thank D. Shimizu for his technical support with electron microscopic imaging.

Funding

This work was supported in part by grants from the Japan Society for the Promotion of Science to S.K. (No. 21K09324).

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Author notes

  1. Farzana Khan and Sakirul Khan equally contributed to this work and shared the first authorship.

Authors and Affiliations

  1. Research Center for Global and Local Infectious Diseases, Oita University, Yufu, Oita, 879-5593, Japan

    Farzana Khan, Sakirul Khan, Hitomi Mimuro & Akira Nishizono

  2. Department of Developmental Biology and Functional Genomics, Ehime University Graduate School of Medicine, Toon, Ehime, 791-0295, Japan

    Farzana Khan, Sakirul Khan, Hiroaki Nabeka & Seiji Matsuda

  3. Department of Microbiology, Faculty of Medicine, Oita University, Yufu, Oita, 879-5593, Japan

    Sakirul Khan & Akira Nishizono

  4. Department of Physiological Chemistry, College of Pharmaceutical Sciences, School of Clinical Pharmacy, Matsuyama University, Matsuyama, Ehime, 790-8578, Japan

    Hiroaki Nabeka

  5. Department of Human Anatomy, Faculty of Medicine, Oita University, Yufu, Oita, 879-5593, Japan

    Fumihiko Hamada

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  1. Farzana Khan
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Correspondence to Sakirul Khan.

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Khan, F., Khan, S., Nabeka, H. et al. Neurotoxic stimulation alters prosaposin levels in the salivary systems of rats. Cell Tissue Res 395, 159–169 (2024). https://doi.org/10.1007/s00441-023-03847-6

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