Your browser doesn't support javascript.
loading
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.
Afiliación
  • Kojima M; Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1-8-31 Midorioka, Ikeda, Osaka 563-8577, Japan.
  • Otabi H; Core Research for Evolutional Science and Technology (CREST), Kawaguchi 332-0012, Japan.
  • Kumanogoh H; Graduate School of Frontier Bioscience, Osaka University, Suita 565-0871, Japan.
  • Toyoda A; College of Agriculture, Ibaraki University, Ami, Ibaraki 300-0393, Japan.
  • Ikawa M; Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1-8-31 Midorioka, Ikeda, Osaka 563-8577, Japan.
  • Okabe M; Core Research for Evolutional Science and Technology (CREST), Kawaguchi 332-0012, Japan.
  • Mizui T; College of Agriculture, Ibaraki University, Ami, Ibaraki 300-0393, Japan.
Int J Mol Sci ; 21(11)2020 Jun 01.
Article en En | MEDLINE | ID: mdl-32492978
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.
Asunto(s)
Palabras clave

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Conducta Animal / Factor Neurotrófico Derivado del Encéfalo / Depresión Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: Int J Mol Sci Año: 2020 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Conducta Animal / Factor Neurotrófico Derivado del Encéfalo / Depresión Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: Int J Mol Sci Año: 2020 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Suiza