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Int. J. Mol. Sci. 2017, 18(9), 1902; doi:10.3390/ijms18091902

Salivary Gland Derived BDNF Overexpression in Mice Exerts an Anxiolytic Effect

1
Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka, Yokosuka, Kanagawa 238-8580, Japan
2
Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 708-0813, Japan
3
Health Promotion and Preemptive Medicine, Research and Development Center for Minimally Invasive Therapies, Tokyo Medical University, Sinjuku, Tokyo 100-0001, Japan
4
School of Dental Hygiene, Department of Junior College, Kanagawa Dental University, Yokosuka, Kanagawa 238-8580, Japan
5
Department of Highly Advanced Stomatology, Yokohama, Kanagawa Dental University, Graduate School of Dentistry, Yokohama, Kanagawa 221-0835, Japan
6
Department of Pathology, Tsurumi University School of Dental Medicine, Yokohama, Kanagawa 238-8580, Japan
7
Department of Pharmaceutical Sciences, Nihon Pharmaceutical University, Kitaadachi, Saitama 335-0021, Japan
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 31 July 2017 / Revised: 30 August 2017 / Accepted: 31 August 2017 / Published: 5 September 2017
(This article belongs to the Special Issue Brain-Derived Neurotrophic Factor)
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Abstract

Brain-derived neurotrophic factor (BDNF) is abundant in the hippocampus and plays critical roles in memory and synapse formation, as well as exerting antidepressant-like effects in psychiatric disorders. We previously reported that BDNF is expressed in salivary glands and affects blood BDNF content. However, the function of salivary BDNF remains unclear. The aim of this study was to generate transgenic mice overexpressing BDNF in the salivary glands. Hence, we used the Lama construct (hemagglutinin (HA)-tagged mouse Bdnf cDNA) to specifically express BDNF in mouse salivary glands. Compared with control mice, Bdnf-HA transgenic mice showed increased blood BDNF and expressed salivary BDNF-HA. Molecular analysis revealed enhanced hippocampal BDNF levels and activation of the BDNF receptor, tyrosine kinase B (TrkB), in transgenic mice. In both the open field and elevated-plus maze tests, transgenic mice showed anxiolytic-like behavioral effects compared with control or sialoadenectomized mice. Among downstream components of the BDNF-TrkB signaling pathway, metabolic activation of the γ-aminobutyric acid (GABA) synthetic pathway was found, including higher levels of the GABA synthetic enzyme, glutamate decarboxylase 1 (GAD1). Thus, we have established a transgenic mouse expressing BDNF in the parotid gland that may be useful to examine the hippocampal effects of salivary BDNF. View Full-Text
Keywords: BDNF; transgenic mouse; hippocampus; saliva; salivary gland; TrkB; anxiolytic BDNF; transgenic mouse; hippocampus; saliva; salivary gland; TrkB; anxiolytic
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MDPI and ACS Style

Saruta, J.; To, M.; Sugimoto, M.; Yamamoto, Y.; Shimizu, T.; Nakagawa, Y.; Inoue, H.; Saito, I.; Tsukinoki, K. Salivary Gland Derived BDNF Overexpression in Mice Exerts an Anxiolytic Effect. Int. J. Mol. Sci. 2017, 18, 1902.

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