Abnormal gene expression of BDNF, but not BDNF-AS, in iPSC, neural stem cells and postmortem brain samples from bipolar disorder

Tamaki Ishima; Sebastian Illes; Yoshimi Iwayama; Brian Dean; Takeo Yoshikawa; Hans Ågren; Keiko Funa; Kenji Hashimoto

doi:10.1016/j.jad.2021.04.042

Abnormal gene expression of BDNF, but not BDNF-AS, in iPSC, neural stem cells and postmortem brain samples from bipolar disorder

J Affect Disord. 2021 Jul 1:290:61-64. doi: 10.1016/j.jad.2021.04.042. Epub 2021 May 3.

Authors

Tamaki Ishima¹, Sebastian Illes², Yoshimi Iwayama³, Brian Dean⁴, Takeo Yoshikawa⁵, Hans Ågren², Keiko Funa⁶, Kenji Hashimoto⁷

Affiliations

¹ Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan.
² Institute of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
³ Laboratory of Molecular Psychiatry, RIKEN Center for Brain Science, Wako, Saitama, Japan; Support Unit for Bio-Material Analysis, Research Resources Division, RIKEN Center for Brain Science, Wako, Saitama, Japan.
⁴ The Florey Institute of Neuroscience and Mental Health, Howard Florey Laboratories, The University of Melbourne, Parkville, Victoria, Australia; The Centre for Mental Health, Swinburne University, Hawthorn, Victoria, Australia.
⁵ Laboratory of Molecular Psychiatry, RIKEN Center for Brain Science, Wako, Saitama, Japan.
⁶ Sahlgrenska Cancer Center, Institute of Biomedicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Oncology Laboratory, Department of Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden.
⁷ Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan. Electronic address: hashimoto@faculty.chiba-u.jp.

PMID: 33993081
DOI: 10.1016/j.jad.2021.04.042

Abstract

Background: Brain-derived neurotrophic factor (BDNF) antisense RNA (BDNF-AS) was identified as naturally conserved non-coding antisense RNA that suppresses the transcription of BDNF.

Methods: We measured the expression of BDNF mRNA and BDNF-AS mRNA in iPSC and NSC from bipolar disorder (BD) patients and healthy control subjects, and postmortem brain samples such as the corpus callosum, the Brodmann area (BA8), and BA46 from BD patients and age- and sex-matched controls.

Results: The expression of BDNF mRNA in iPSC from BD patients (n = 6) was significantly lower than that of control subjects (n = 4) although the expression of BDNF mRNA in NSC from BD patients was significantly higher than that of control subjects. In contrast, there were no changes in the expression of BDNF-AS mRNA in both iPSC and NSC between two groups. The expression of BDNF mRNA in the BA46 from BD patients (n = 35) was significantly lower than that of controls (n = 34) although the expression of BDNF mRNA in the corpus callosum and BA8 was not different between two groups (n = 15). In contrast, there were no changes in expression of BDNF-AS mRNA in the three brain regions between two groups. Interestingly, there were significant positive correlations between BDNF mRNA expression and BDNF-AS mRNA expression in the postmortem brain samples.

Limitations: Sample sizes are relatively low.

Conclusions: Our data suggest that abnormalities in the expression of BDNF, but not BDNF-AS, play a role in the pathogenesis of BD.

Keywords: BDNF; BDNF antisense; Long non-coding RNA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bipolar Disorder* / genetics
Brain / metabolism
Brain-Derived Neurotrophic Factor / genetics
Brain-Derived Neurotrophic Factor / metabolism
Gene Expression
Humans
Induced Pluripotent Stem Cells* / metabolism
Neural Stem Cells* / metabolism

Substances

Brain-Derived Neurotrophic Factor
BDNF protein, human