Scientists have learned a lot about mental health conditions such as autism spectrum disorder, schizophrenia, and Alzheimer’s disease.
They have discovered many genetic changes and problems with how certain proteins work in the brain. These findings have helped us understand these conditions better.
But there are still some brain proteins whose roles remain unclear. One of these lesser‑known proteins is called indoleamine 2,3-dioxygenase 2, or IDO2.
IDO2 belongs to a chemical pathway in the brain called the tryptophan–kynurenine pathway. This pathway helps the body process tryptophan, an amino acid found in foods like eggs, meat, dairy, and nuts.
Scientists pay close attention to this pathway because some of its products have been linked to psychiatric conditions, including autism and mood disorders. But until recently, nobody knew exactly what IDO2 was doing in the brain.
To explore this mystery, Associate Professor Yasuko Yamamoto and her team at Fujita Health University in Japan performed a study using mice. Their research, published in The FEBS Journal, compared normal mice to special genetically modified mice that completely lacked the IDO2 gene.
These modified animals are called IDO2 knock‑out mice. By removing IDO2 entirely, the researchers could observe how the brain behaved without it.
The results were surprising. The mice without IDO2 showed behaviors that looked similar to traits seen in autism. They had trouble adjusting to new environments and became stressed more easily.
They also repeated certain actions, such as grooming themselves over and over again. When placed in a new space, they explored less and showed little interest in unfamiliar surroundings.
The researchers also tested social learning, which is an important part of how animals, including humans, interact with others and learn from them. The IDO2 knock‑out mice struggled to learn from other mice. Their behavior showed difficulties with flexibility and social interaction—two areas often affected in autism.
To understand why these behaviors were happening, the team examined the mice’s brain chemistry. They discovered that without IDO2, the tryptophan–kynurenine pathway functioned differently. This change affected dopamine levels in key parts of the brain, such as the striatum and the amygdala.
Dopamine is a chemical messenger that helps control mood, motivation, reward, and learning. When dopamine signaling is disturbed, it can lead to problems with behavior, emotions, and learning.
Another major finding involved a molecule called brain-derived neurotrophic factor, or BDNF. BDNF is essential for keeping brain cells healthy. It helps neurons grow, form new connections, and stay adaptable throughout life.
In the mice without IDO2, BDNF levels were lower. When the researchers looked at the mice’s brain cells under a microscope, they saw fewer mature dendritic spines. These tiny structures help neurons communicate with each other. More immature spines suggested that the brain was not forming strong, healthy connections.
The team also studied microglia, which act as the brain’s maintenance cells. Normally, many microglia stay in a calm “surveillant” state, monitoring and cleaning up the brain in a gentle way. But in the mice without IDO2, many microglia changed into a more aggressive form called “ameboid.”
These cells break down damaged material more actively, which can affect how brain circuits develop. Combined with the lower BDNF levels, this shift may explain why the mice behaved differently.
To test whether IDO2 could reverse these effects, the researchers restored IDO2 in the knock‑out mice. The result was remarkable. The mice started behaving more like normal mice, suggesting that IDO2 plays an important role in maintaining healthy brain function and behavior.
This discovery hints that IDO2 might be involved in some of the biological processes affected in autism and other mental health conditions.
The researchers then looked at human data to see if IDO2 might also matter for people. In brain samples from 309 individuals with autism, they found a rare mutation in the IDO2 gene in a 16‑year‑old girl. Although this was just one case, it suggests that IDO2 may also play a part in autism in humans, and it gives scientists a new direction to explore.
This research opens a new door in understanding the biology of autism and other psychiatric conditions. Although much more research is needed, these findings point to IDO2 as a possible target for new treatments. Learning more about this mysterious protein could help doctors develop better therapies to support brain health.
For families interested in autism, researchers are also studying how lifestyle factors may help. Some studies suggest that pet cats may reduce anxiety in children with autism. Other studies are looking at how certain foods and nutrients affect the brain.
Together, these discoveries offer hope for better ways to understand, support, and care for people with autism and other mental health conditions.
If you care about Alzheimer’s disease, please read studies about the protective power of dietary antioxidants against Alzheimer’s, and eating habits linked to higher Alzheimer’s risk.
For more health information, please see recent studies that oral cannabis extract may help reduce Alzheimer’s symptoms, and Vitamin E may help prevent Parkinson’s disease.
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