Salivary Gland Derived BDNF Overexpression in Mice Exerts an Anxiolytic Effect

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.