Reduction in BDNF from inefficient precursor conversion influences nest building and promotes depressive-like behavior in mice

Kojima, Masami; Otabi, Hikari; Kumanogoh, Haruko; Toyoda, Atsushi; Ikawa, Masahito; Okabe, Masaru; Mizui, Toshiyuki

doi:https://doi.org/10.3390/ijms21113984

Reduction in BDNF from inefficient precursor conversion influences nest building and promotes depressive-like behavior in mice

Kojima, Masami; Otabi, Hikari; Kumanogoh, Haruko et al.

International Journal of Molecular Sciences, 2020, 21(11), 3984

Number of Access:801（2025-08-22 01:04 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/78545

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Title	Reduction in BDNF from inefficient precursor conversion influences nest building and promotes depressive-like behavior in mice
Creator	NRID 1000040344171 1000040344171 CreatorName Kojima, Masami
	CreatorName Otabi, Hikari
	CreatorName Kumanogoh, Haruko
	NRID 1000000292483 1000000292483 CreatorName Toyoda, Atsushi
	NRID 1000020304066 1000020304066 ORCID 0000-0001-9859-6217 0000-0001-9859-6217 researchmap permalink read0054910 read0054910 Scopus Author ID 16689054500 16689054500 CreatorName Ikawa, Masahito
	NRID 1000030089875 1000030089875 CreatorName Okabe, Masaru
	CreatorName Mizui, Toshiyuki
Subject	BDNF
	Cleavage
	Depression
	Nest building
	SNP
	Social isolation
Description	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
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 nestbuilding behaviors. These findings suggest that the decreased production of mBDNF by impaired proBDNF cleavage disturbs daily activities in mice.
Publisher	MDPI
Source Title	International Journal of Molecular Sciences
Volume (Issue)	21(11)
Page	3984
Date of Issued	2020-06-01
Language	English
Handle URL	https://hdl.handle.net/11094/78545
PISSN	16616596
eISSN	14220067
NCID	AA12038549
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.3390/ijms21113984
Relation.isIdenticalTo	PMID 32492978
Access Rights	open access
CopyRight	© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCTERMS.bibliographicCitation	International Journal of Molecular Sciences. 2020, 21(11), p. 3984
DC.title	Reduction in BDNF from inefficient precursor conversion influences nest building and promotes depressive-like behavior in mice
DC.creator	Kojima, Masami
	Otabi, Hikari
	Kumanogoh, Haruko
	Toyoda, Atsushi
	Ikawa, Masahito
	Okabe, Masaru
	Mizui, Toshiyuki
DC.publisher	MDPI
DC.language' scheme='DCTERMS.RFC1766	English
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2020-06-01
DC.identifier	https://doi.org/10.3390/ijms21113984
DC.subject	BDNF
	Cleavage
	Depression
	Nest building
	SNP
	Social isolation
DC.description	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
DCTERMS.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 nestbuilding behaviors. These findings suggest that the decreased production of mBDNF by impaired proBDNF cleavage disturbs daily activities in mice.
DC.rights	© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	78545
citation_title	Reduction in BDNF from inefficient precursor conversion influences nest building and promotes depressive-like behavior in mice
citation_author	Kojima, Masami
	Otabi, Hikari
	Kumanogoh, Haruko
	Toyoda, Atsushi
	Ikawa, Masahito
	Okabe, Masaru
	Mizui, Toshiyuki
citation_publisher	MDPI
citation_language	English
citation_date	2020-06-01
citation_journal_title	International Journal of Molecular Sciences
citation_volume	21
citation_issue	11
citation_firstpage	3984
citation_doi	https://doi.org/10.3390/ijms21113984
citation_pmid	32492978
citation_public_url	https://hdl.handle.net/11094/78545

Reduction in BDNF from inefficient precursor conversion influences nest building and promotes depressive-like behavior in mice

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