PMID- 28872625
OWN - NLM
STAT- MEDLINE
DCOM- 20180514
LR  - 20181113
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 18
IP  - 9
DP  - 2017 Sep 5
TI  - Salivary Gland Derived BDNF Overexpression in Mice Exerts an Anxiolytic Effect.
LID - 10.3390/ijms18091902 [doi]
LID - 1902
AB  - 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 gamma-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.
FAU - Saruta, Juri
AU  - Saruta J
AD  - Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental 
      University, 82 Inaoka, Yokosuka, Kanagawa 238-8580, Japan. saruta@kdu.ac.jp.
FAU - To, Masahiro
AU  - To M
AD  - Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental 
      University, 82 Inaoka, Yokosuka, Kanagawa 238-8580, Japan. m.tou@kdu.ac.jp.
FAU - Sugimoto, Masahiro
AU  - Sugimoto M
AD  - Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental 
      University, 82 Inaoka, Yokosuka, Kanagawa 238-8580, Japan. msugi@sfc.keio.ac.jp.
AD  - Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 708-0813, 
      Japan. msugi@sfc.keio.ac.jp.
AD  - Health Promotion and Preemptive Medicine, Research and Development Center for 
      Minimally Invasive Therapies, Tokyo Medical University, Sinjuku, Tokyo 100-0001, 
      Japan. msugi@sfc.keio.ac.jp.
FAU - Yamamoto, Yuko
AU  - Yamamoto Y
AD  - School of Dental Hygiene, Department of Junior College, Kanagawa Dental 
      University, Yokosuka, Kanagawa 238-8580, Japan. yuko@yd6.so-net.ne.jp.
FAU - Shimizu, Tomoko
AU  - Shimizu T
AD  - Department of Highly Advanced Stomatology, Yokohama, Kanagawa Dental University, 
      Graduate School of Dentistry, Yokohama, Kanagawa 221-0835, Japan. 
      shimizu@kdu.ac.jp.
FAU - Nakagawa, Yusuke
AU  - Nakagawa Y
AD  - Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental 
      University, 82 Inaoka, Yokosuka, Kanagawa 238-8580, Japan. 
      yusuke_2828@yahoo.co.jp.
FAU - Inoue, Hiroko
AU  - Inoue H
AD  - Department of Pathology, Tsurumi University School of Dental Medicine, Yokohama, 
      Kanagawa 238-8580, Japan. inoue-h@nichiyaku.ac.jp.
AD  - Department of Pharmaceutical Sciences, Nihon Pharmaceutical University, 
      Kitaadachi, Saitama 335-0021, Japan. inoue-h@nichiyaku.ac.jp.
FAU - Saito, Ichiro
AU  - Saito I
AD  - Department of Pathology, Tsurumi University School of Dental Medicine, Yokohama, 
      Kanagawa 238-8580, Japan. saito-i@tsurumi-u.ac.jp.
FAU - Tsukinoki, Keiichi
AU  - Tsukinoki K
AD  - Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental 
      University, 82 Inaoka, Yokosuka, Kanagawa 238-8580, Japan. tsukinoki@kdu.ac.jp.
LA  - eng
PT  - Journal Article
DEP - 20170905
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Anti-Anxiety Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 4.1.1.15 (Glutamate Decarboxylase)
RN  - EC 4.1.1.15 (glutamate decarboxylase 1)
SB  - IM
MH  - Animals
MH  - Anti-Anxiety Agents/metabolism
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Glutamate Decarboxylase/metabolism
MH  - Hippocampus/metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Protein-Tyrosine Kinases/metabolism
MH  - Salivary Glands/*metabolism
MH  - gamma-Aminobutyric Acid/metabolism
PMC - PMC5618551
OTO - NOTNLM
OT  - BDNF
OT  - TrkB
OT  - anxiolytic
OT  - hippocampus
OT  - saliva
OT  - salivary gland
OT  - transgenic mouse
COIS- The authors declare no conflict of interest.
EDAT- 2017/09/06 06:00
MHDA- 2018/05/15 06:00
PMCR- 2017/09/01
CRDT- 2017/09/06 06:00
PHST- 2017/07/31 00:00 [received]
PHST- 2017/08/30 00:00 [revised]
PHST- 2017/08/31 00:00 [accepted]
PHST- 2017/09/06 06:00 [entrez]
PHST- 2017/09/06 06:00 [pubmed]
PHST- 2018/05/15 06:00 [medline]
PHST- 2017/09/01 00:00 [pmc-release]
AID - ijms18091902 [pii]
AID - ijms-18-01902 [pii]
AID - 10.3390/ijms18091902 [doi]
PST - epublish
SO  - Int J Mol Sci. 2017 Sep 5;18(9):1902. doi: 10.3390/ijms18091902.