Salivary Gland Derived BDNF Overexpression in Mice Exerts an Anxiolytic Effect

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.

Effect of social isolation stress on saliva BDNF in rat

“…administration), following injection of pilocarpine-HCl (1 mg/kg, i.p. ; Sanpilo 1%; Santen Pharmaceutical Co., Ltd., Osaka, Japan) [3]. Following this, the rats were euthanized.…”

“…The OF tests were performed as described previously [3]. Briefly, the experimental space was surrounded by a black curtain, and illumination was provided by a fluorescent light (light intensity, 23-25 lux).…”

“…They work as an endocrine and exocrine organ because some of the secreted products are transferred into the bloodstream via endocrine mechanisms [2]. Neurotrophins, including nerve growth factor and brain-derived neurotrophic factor (BDNF), are secreted by salivary glands and can exert hormone-like effects on organs distant from the salivary glands, such as the brain [3] and adrenal gland [4]. Importantly, the salivary glands are sensitive to stress [5], and saliva may contain biomarkers associated with stress-related disease [6].…”

“…Additionally, changes in blood metabolites have been observed in response to social isolation stress [8]. A previous study has reported that compounds found in saliva are related to brain function by affecting metabolites in the hippocampus [3]. However, the relationship between social isolation stress and compounds present in saliva remains unclear.…”

A Newly Created Meso-, Micro-, and Nano-Scale Rough Titanium Surface Promotes Bone-Implant Integration

“…Total RNA was isolated at days 7 and 14 using an RNeasy Plus Mini Kit (Qiagen, Hilden, Germany) and complementary DNA (cDNA) was made as described previously [62]. Real-time qPCR was performed in triplicate for each sample with LC480 SYBR Green I Master (Roche Diagnostics, Indianapolis, IN, USA) using universal cycling conditions on a LightCycler 480 (Roche) [63]. A total of 55 cycles were executed and the second derivative Cq value determination method was used to compare fold-differences.…”