Identification of mtDNA mutations associated with bipolar-like behaviour in CaMKIIa-Polg1 mice using Ultra-Deep Next-Generation Sequencing

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K15531
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Bagge Emilie 国立研究開発法人理化学研究所, 脳神経科学研究センター, 研究員 (30813795)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: mitochondria / mtdna / bipolar disorder / sequencing / epigenetics

Outline of Final Research Achievements

Mutations in mitochondrial genes have been found in some patients with bipolar disorder (BD). Mitochondria are the energy-producing units of the cell and without functional mitochondria the cell itself is at risk of dysfunction. Mutations in mitochondrial genes are thought to cause mutations in a specific type of DNA, mtDNA, that is present within mitochondria.
In this research project we implemented a method that allows us to look at all mutations in mtDNA from very small pieces of tissue, and thereby create a "brain-wide view" of mtDNA mutations. By analysing the brains of mice that have a mutation in a mitochondrial gene found in BD patients, we found that specific brain regions are very sensitive to have mutations. These brain regions have previously been found to be involved in BD. This indicates that mitochondria and mitochondrial regulation is different across brain regions and may contribute to neuropsychiatric disorders.

Free Research Field

Neuroscience

Academic Significance and Societal Importance of the Research Achievements

The method we have implemented allows us to examine mtDNA from smaller tissue pieces than previously without the need for biasing approaches. Our brain-wide view of mtDNA mutations add new depth to mitochondrial research and better our understanding of the molecular mechanisms of bipolar disorder.