Unknown

Dataset Information

0

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


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.

SUBMITTER: Kojima M 

PROVIDER: S-EPMC7312902 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Kojima Masami M   Otabi Hikari H   Kumanogoh Haruko H   Toyoda Atsushi A   Ikawa Masahito M   Okabe Masaru M   Mizui Toshiyuki T  

International journal of molecular sciences 20200601 11


We generated a knock-in mouse line in which the gene encoding brain-derived neurotrophic factor (<i>Bdnf</i>) 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 proteolyt  ...[more]

Similar Datasets

| S-EPMC10455050 | biostudies-literature
| S-EPMC7552269 | biostudies-literature
| S-EPMC8907159 | biostudies-literature
| S-EPMC6750640 | biostudies-literature
| S-EPMC4183950 | biostudies-literature
| S-EPMC4858914 | biostudies-literature
| S-EPMC4822453 | biostudies-other
| S-EPMC3748181 | biostudies-other
| S-EPMC3361010 | biostudies-literature
| S-EPMC5333539 | biostudies-literature