In recent years, scientists have made progress in understanding psychiatric disorders like autism spectrum disorder (ASD), schizophrenia, and Alzheimer’s disease. Research has revealed certain genetic changes and protein imbalances that may contribute to these conditions.
However, there’s still a lot we don’t know about the proteins involved in brain function. One of these is a protein called indoleamine 2,3-dioxygenase 2 (IDO2), which is processed through a brain pathway known as the tryptophan–kynurenine pathway (TKP).
The TKP, along with its byproducts, has been linked to various psychiatric disorders, but scientists have been uncertain about the exact role of IDO2 in the brain.
To learn more, Associate Professor Yasuko Yamamoto and her team at Fujita Health University in Japan conducted a study, published in The FEBS Journal, exploring IDO2’s influence on behavior by studying genetically modified mice that lack this protein.
The researchers began by observing two groups of mice: normal mice and genetically modified mice missing the IDO2 gene, known as IDO2 knock-out (KO) mice. They found that the IDO2 KO mice showed behaviors similar to those seen in autism.
For instance, these mice struggled with adapting to new environments, displayed repetitive behaviors like excessive grooming, and showed little interest in exploring their surroundings.
When tested for social behaviors, these mice also struggled to learn from other mice, a key aspect of social interaction that is often affected in ASD.
Looking closer at the biochemical changes caused by the absence of IDO2, the researchers discovered changes in the levels of tryptophan metabolites, which are chemicals produced through the TKP.
One of the most important findings was how these changes impacted dopamine, a chemical messenger that plays a key role in motivation, pleasure, and social behavior.
In the IDO2 KO mice, the researchers noticed a disruption in dopamine activity within two specific areas of the brain—the striatum and the amygdala. These regions are known for their roles in regulating emotions, motivation, and social behaviors.
In addition to this dopamine imbalance, the IDO2 KO mice had lower levels of certain molecules involved in dopamine signaling.
This included brain-derived neurotrophic factor (BDNF), a protein essential for neuron growth and brain flexibility, known as neuroplasticity. BDNF helps the brain adapt to changes, which is crucial for learning and behavior.
When the scientists examined the structure of neurons in the IDO2 KO mice, they found a higher density of immature dendritic spines—tiny structures on neurons that help with cell-to-cell communication.
Another important finding was a shift in the behavior of microglia, the brain’s immune cells that usually clear out extra connections during brain development.
In the IDO2 KO mice, these microglia switched from their normal “watchful” state to an active state associated with higher levels of brain inflammation. Together, these changes may contribute to the ASD-like behaviors observed in these mice.
An interesting part of the study came when the researchers tried to restore IDO2 levels in the genetically modified mice.
After a chemical treatment to reintroduce IDO2, the mice’s behavior became more similar to that of the normal mice, suggesting that IDO2 plays a key role in regulating these behaviors.
Furthermore, when the researchers examined the brains of individuals with ASD, they found an IDO2 gene mutation in one of the cases—a 16-year-old girl with ASD. While this is just one case, it points to a possible link between IDO2 and autism.
This research provides a new perspective on the role of IDO2 and the TKP pathway in brain development and behavior.
By studying how IDO2 influences the brain’s chemistry and cellular structure, scientists may be closer to understanding some of the biological mechanisms underlying autism and potentially other psychiatric disorders.
Although more research is needed, this study offers important insights and could help guide future treatment options for conditions like autism.
For those interested in learning more about autism, some studies suggest that pets, such as cats, may help reduce anxiety in children with ASD, and ongoing research aims to improve treatment options.
Additionally, studies have shown that diet can influence brain health, and certain foods might even affect autism risk.
The complete research findings are published in The FEBS Journal.
If you care about autism, please read studies that cats may help decrease anxiety for kids with autism and new study may develop better treatment for autism
For more information about health, please see recent studies about how to eat your way to a healthy brain, and results showing this type of food may contribute to autism.
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