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Professor Tadafumi Kato and his team were recently covered in an advertisement feature in Nature Index: Neuroscience in an article that discusses their ground-breaking work shedding light on the brain regions and mechanisms involved in bipolar disorder.

 

In a research effort spanning three decades, Professor Tadafumi Kato and his team at Juntendo University have identified the paraventricular nucleus of the thalamus as a potential origin of bipolar disorder and elucidated the underlying mechanisms involved. Their research is paving the way for more accurate diagnoses and targeted treatments that could improve a patient’s quality of life.

 

Juntendo University Makes Waves in Neuroscience: Professor Kato Is Covered in an Advertisement Feature Nature Index: Neuroscience

Image caption: Professor Tadafumi Kato and his team at Juntendo University are covered in an advertisement feature in Nature Index: Neuroscience for their pioneering research on brain regions and mechanisms involved in bipolar disorder

Image credit: Dr. Tadafumi Kato from Juntendo University, Japan

License type: Original content

Usage restrictions: You are free to share and adapt the Infographic material but attribution is required, with a link to the news source.

 

Patients with bipolar I and bipolar II disorders typically experience extreme mood swings, shifting from emotional highs or mania to depressive lows. Bipolar disorder (BD) is also associated with a high risk of suicide—about 30 times greater than that of the general population. Unfortunately, despite the availability of medication and other treatment methods that manage these symptoms to some extent, the biological causes of BD remain an unsolved mystery.

 

Now, Professor Tadafumi Kato and his team at Juntendo University in Tokyo believe they may have identified the brain regions involved in this disorder. Prof. Kato’s research on mood disorders spans more than three decades and has shed light on a key question: while we know that patients with mood disorders experience intense positive and negative emotions, where exactly do these feelings originate from? The answer may lie in the paraventricular nucleus of the thalamus (PVT)—an elusive region deep inside the brain. It turns out that the PVT may play a central role in BD and the intense mood swings that accompany it.

 

For their work in recognizing the brain regions responsible for BD symptoms, Kato and his laboratory are leading their field globally. The advertisement feature in Nature Index: Neuroscience describes this pioneering research on BD and how it enhances our understanding of the mechanisms involved.

 

What inspired Kato to identify the brain regions and mechanisms involved in BD? As early as 2000, he had discovered that patients with BD had dysfunctional mitochondria in their brains. Kato and his team found more compelling evidence in a subsequent study in 2016, which revealed that dysfunctional mitochondria accumulated in the PVT of the brains of model mice. Further experiments showed that manipulating PVT function in mice led to symptoms of repeated depressive episodes, indicating that this region significantly contributed to BD symptoms.

 

The next step was to determine exactly how mitochondrial dysfunction in the PVT caused symptoms of BD. According to Dr. Mie Kubota-Sakashita, a neuroscientist at Juntendo University, changes in calcium signaling may be crucial. She discovered that in the brains of mice genetically engineered to exhibit symptoms similar to those of BD, their mitochondria showed altered patterns of calcium uptake. This mechanism could explain the ‘swinging pendulum’ of extreme emotions associated with BD.

 

BD is known to have a strong genetic component—individuals with a family history of BD have a higher risk of developing it themselves. According to Associate Professor Masaki Nishioka, a neurogeneticist in the Department of Psychiatry at Juntendo University, the genes responsible for BD are still poorly understood. “There’s not much influence from individual genes,” said Nishioka in the advertisement feature. “Rather, the symptoms appear to arise from a complex interaction of many genes.” Nishioka believes that new sequencing techniques, which analyze gene expression down to the level of a single nucleus, will provide exciting insights into the genetic basis of BD.

 

The research on BD at Juntendo also has far-reaching implications for the diagnosis and treatment of BD. Identifying the role of the PVT may lead to more precise diagnostic methods. “Currently, we have no choice but to diagnose many mental disorders based on subjective experiences and behaviors, rather than on what is happening at the biological level. It’s as if we were diagnosing diabetes through symptoms such as lethargy and thirst, without measuring blood sugar and insulin,” said Kato in the advertisement feature.

 

Besides improving our understanding of current treatments like mood-stabilizing drugs, uncovering the mechanisms involved in BD opens avenues for new treatment options, such as using existing drugs to enhance calcium uptake by mitochondria.

 

The future of BD research looks promising as Kato’s work brings us one step closer to understanding a mood disorder that has long been a mystery to the scientific community.

 

The advertisement feature, “Searching for the biology behind bipolar disorders,” was published on October 3, 2024, in the print and online version of Nature, a weekly international comprehensive science journal. The article is a part of the Nature Index collection on neuroscience, and can be accessed here: https://www.nature.com/articles/d42473-024-00245-6.

Nature Index: Neuroscience is here: https://www.nature.com/collections/jbdiafadhj

 

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References

 

Title of original paper: Depression-like episodes in mice harboring mtDNA deletions in paraventricular thalamus

Journal: Molecular Psychiatry

DOI: https://doi.org/10.1038/mp.2015.156

 

Title of original paper: Deep exome sequencing identifies enrichment of deleterious mosaic variants in neurodevelopmental disorder genes and mitochondrial tRNA regions in bipolar disorder

Journal: Molecular Psychiatry

DOI: https://doi.org/10.1038/s41380-023-02096-x

 

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About Professor Tadafumi Kato

Dr. Tadafumi Kato is a Professor at the Department of Psychiatry and Behavioral Science, as well as the Director of the Center for Mood Disorders at Juntendo University. His research focuses on the neurobiological basis of bipolar disorder, encompassing exome sequencing, neuroimaging, and the development of mood stabilizers. With over 35 years of experience, Prof. Kato has authored 289 original articles and 40 review articles. His notable achievements include leadership roles at the RIKEN Brain Science Institute and the RIKEN Center for Brain Science in the past.