In recent years, scientists have made big strides in understanding mental health conditions like autism spectrum disorder (ASD), schizophrenia, and Alzheimer’s disease. They’ve found certain genetic changes and problems with how proteins work in the brain that may contribute to these conditions.
Even with all these advancements, there are still some brain proteins that remain a mystery. One of these is a protein called indoleamine 2,3-dioxygenase 2, or IDO2.
This protein is part of a chemical pathway in the brain called the tryptophan–kynurenine pathway (TKP), which processes tryptophan, an amino acid found in many foods. The TKP is important because its products have been linked to several psychiatric conditions.
To understand how IDO2 might be involved in these disorders, Associate Professor Yasuko Yamamoto and her research team at Fujita Health University in Japan conducted a study using mice.
Their research, which was published in The FEBS Journal, compared normal mice with genetically modified mice that did not have the IDO2 gene. These modified mice are called IDO2 knock-out (KO) mice. The researchers wanted to see if the absence of IDO2 would affect the behavior and brain chemistry of these mice.
The results were striking. The IDO2 KO mice showed behaviors that are similar to symptoms seen in people with autism. For example, they had trouble adapting to new environments, spent a lot of time doing repetitive grooming, and seemed less interested in exploring their surroundings.
When the researchers tested the mice’s social behavior, they found that the IDO2 KO mice had a hard time learning from other mice. These are all behaviors that reflect difficulties in social interaction and adaptability—common traits in autism.
The researchers then dug deeper to understand why these behaviors were happening. They studied the brain chemistry of the mice and found that the absence of IDO2 changed the way certain chemicals were processed in the TKP.
This, in turn, affected dopamine levels in key areas of the brain, like the striatum and the amygdala. Dopamine is important for mood regulation, motivation, and learning. When dopamine signaling is disrupted, it can lead to the kinds of behavioral changes seen in the IDO2 KO mice.
One particularly interesting finding was that the lack of IDO2 reduced the levels of a molecule called brain-derived neurotrophic factor (BDNF). BDNF is crucial for brain health because it helps neurons grow and form new connections. It also plays a role in the brain’s ability to adapt and change, which is known as neuroplasticity.
In the IDO2 KO mice, lower BDNF levels meant their neurons had fewer mature connections. This was visible when the researchers looked at the mice’s brain cells under a microscope—they saw more immature dendritic spines, which are tiny structures on neurons that help them communicate.
The research team also studied microglia, which are special cells in the brain that help maintain neuron health. Microglia have two main forms: one is called the “surveillant” type, which monitors and cleans up unnecessary connections, and the other is the “ameboid” type, which is more active in breaking down damaged cells.
In the IDO2 KO mice, the microglia shifted from the calmer surveillant form to the more aggressive ameboid form. This change, along with the reduction in BDNF, could explain why these mice displayed behaviors similar to autism.
The team then went a step further and tried to restore IDO2 levels in the genetically modified mice. Remarkably, when IDO2 was brought back, the mice’s behaviors became more like those of normal mice. This suggests that IDO2 might play a key role in regulating certain behaviors and brain functions that are affected in psychiatric conditions.
To see if these findings might apply to humans, the researchers looked at brain samples from 309 people with autism. Among these samples, they found one case—a 16-year-old girl—with a mutation in the IDO2 gene. While it is just one example, it hints that IDO2 might also be important in understanding autism in people.
This research provides a new clue in the search to understand the biological roots of autism and other psychiatric disorders. While more research is needed, Associate Professor Yamamoto’s work opens the door to exploring IDO2 as a target for new treatments.
Discovering how this protein affects brain function could one day help doctors develop better therapies for those with mental health conditions.
For those interested in autism and mental health, it’s worth noting that some studies suggest that having a pet cat may help reduce anxiety in children with autism. There are also new studies exploring how certain foods might impact brain health and contribute to autism. These findings bring hope for better understanding and managing these conditions in the future.
If you care about autism, please read studies about a new cause of autism, and cats may help decrease anxiety for kids with autism.
For more information about health, please see recent studies about vitamin D that may hold the clue to more autism, and results showing strange eating habits may signal autism.
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