A novel knockout mouse model of the noncoding antisense Brain-Derived Neurotrophic Factor (Bdnf) gene displays increased endogenous Bdnf protein and improved memory function following exercise

Farzaneh Modarresi, Roya Pedram Fatemi, Seyedeh Fatemeh Razavipour, Natalie Ricciardi, Madina Makhmutova, Nathalie Khoury, Marco Magistri, Claude Henry Volmar, Claes Wahlestedt, Mohammad Ali Faghihi

Research output: Contribution to journalArticlepeer-review

Abstract

Brain-derived neurotrophic factor (Bdnf) expression is tightly controlled at the transcriptional and post-transcriptional levels. Previously, we showed that inhibition of noncoding Bdnf antisense (Bdnf-AS) RNA upregulates Bdnf protein. Here, we generated a Bdnf-antisense knockout (Bdnf-AS KO) mouse model by deleting 6 kilobases upstream of Bdnf-AS. After verifying suppression of Bdnf-AS, baseline behavioral tests indicated no significant difference in knockout and wild type mice, except for enhanced cognitive function in the knockout mice in the Y-maze. Following acute involuntary exercise, Bdnf-AS KO mice were re-assessed and a significant increase in Bdnf mRNA and protein were observed. Following long-term involuntary exercise, we observed a significant increase in nonspatial and spatial memory in novel object recognition and Barnes maze tests in young and aged Bdnf-AS KO mice. Our data provides evidence for the beneficial effects of endogenous Bdnf upregulation and the synergistic effect of Bdnf-AS knockout on exercise and memory retention.

Original languageEnglish (US)
Article numbere07570
JournalHeliyon
Volume7
Issue number7
DOIs
StatePublished - Jul 2021

Keywords

  • Antisense RNA
  • BDNF
  • Exercise
  • Knockout mouse
  • Learning
  • Memory

ASJC Scopus subject areas

  • General

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