論文

査読有り 国際誌
2020年6月1日

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

International journal of molecular sciences
  • Masami Kojima
  • ,
  • Hikari Otabi
  • ,
  • Haruko Kumanogoh
  • ,
  • Atsushi Toyoda
  • ,
  • Masahito Ikawa
  • ,
  • Masaru Okabe
  • ,
  • Toshiyuki Mizui

21
11
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.3390/ijms21113984

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.

リンク情報
DOI
https://doi.org/10.3390/ijms21113984
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32492978
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312902
ID情報
  • DOI : 10.3390/ijms21113984
  • PubMed ID : 32492978
  • PubMed Central 記事ID : PMC7312902

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