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Volume 21
Issue 11
10.3390/ijms21113984
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Article

Reduction in BDNF from Inefficient Precursor Conversion Influences Nest Building and Promotes Depressive-Like Behavior in Mice

by
Masami Kojima
1,2,3,*,†,
Hikari Otabi
4,
Haruko Kumanogoh
1,2,
Atsushi Toyoda
4,
Masahito Ikawa
5,
Masaru Okabe
5 and
Toshiyuki Mizui
1,2,*,†
1
Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1-8-31 Midorioka, Ikeda, Osaka 563-8577, Japan
2
Core Research for Evolutional Science and Technology (CREST), Kawaguchi 332-0012, Japan
3
Graduate School of Frontier Bioscience, Osaka University, Suita 565-0871, Japan
4
College of Agriculture, Ibaraki University, Ami, Ibaraki 300-0393, Japan
5
Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 5650871, Japan
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(11), 3984; https://doi.org/10.3390/ijms21113984
Received: 4 February 2020 / Revised: 17 May 2020 / Accepted: 23 May 2020 / Published: 1 June 2020
(This article belongs to the Section Molecular Neurobiology)
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Abstract

We generated a knock-in mouse line in which the gene encoding brain-derived neurotrophic factor (Bdnf) was replaced with a sequence for proBDNF containing human single nucleotide polymorphisms encoding arginines proximal to the cleavage site (R125M and R127L). The ratio of the mature form of BDNF (mBDNF) to precursor BDNF (proBDNF) in hippocampal tissue lysates was decreased in a manner dependent on the number of copies of the mutant gene, indicating that the mutations inhibited proteolytic conversion of proBDNF into mBDNF. Although homozygous mice had a proBDNF/mBDNF ratio of ~9:1, they survived until adulthood. The levels of mBDNF were reduced by 57% in heterozygous mutant mice, which exhibited a depressive-like behavior in the tail suspension test and weight gain when housed in social isolation, showing that impaired proBDNF cleavage contributes to stress-induced depressive-like phenotypes. Furthermore, socially isolated heterozygous mice displayed a pronounced deficit in daily nest-building behaviors. These findings suggest that the decreased production of mBDNF by impaired proBDNF cleavage disturbs daily activities in mice. View Full-Text
Keywords: BDNF; depression; nest building; cleavage; SNP; social isolation BDNF; depression; nest building; cleavage; SNP; social isolation
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MDPI and ACS Style

Kojima, M.; Otabi, H.; Kumanogoh, H.; Toyoda, A.; Ikawa, M.; Okabe, M.; Mizui, T. Reduction in BDNF from Inefficient Precursor Conversion Influences Nest Building and Promotes Depressive-Like Behavior in Mice. Int. J. Mol. Sci. 2020, 21, 3984. https://doi.org/10.3390/ijms21113984

AMA Style

Kojima M, Otabi H, Kumanogoh H, Toyoda A, Ikawa M, Okabe M, Mizui T. Reduction in BDNF from Inefficient Precursor Conversion Influences Nest Building and Promotes Depressive-Like Behavior in Mice. International Journal of Molecular Sciences. 2020; 21(11):3984. https://doi.org/10.3390/ijms21113984

Chicago/Turabian Style

Kojima, Masami, Hikari Otabi, Haruko Kumanogoh, Atsushi Toyoda, Masahito Ikawa, Masaru Okabe, and Toshiyuki Mizui. 2020. "Reduction in BDNF from Inefficient Precursor Conversion Influences Nest Building and Promotes Depressive-Like Behavior in Mice" International Journal of Molecular Sciences 21, no. 11: 3984. https://doi.org/10.3390/ijms21113984

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