Light-sensing Protein Could Explain Seasonal Changes in MS Risk

The presence of a light-sensing protein in the brain during the early stages of fetal development may help to explain why certain neurological diseases, like multiple sclerosis (MS), are more common among people born at specific times of the year, a study found.

The researchers, who noted that people born in the springtime are more likely to develop MS in adulthood, said their findings suggest a link between light exposure during pregnancy and the development of an unborn baby’s brain.

“Ultimately, this discovery may open up possibilities for using the right kind of light stimulation during pregnancy to reduce the risk of neurological disorders in adulthood,” Lena Gunhaga, a professor at Umeå University, in Sweden and a study co-author, said in a press release.

“Although more research is required before we can issue recommendations about specific light therapies for pregnant women, we are clearly on an exciting track that may eventually prove highly significant,” Gunhaga said.

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These results were published in eNeuro, in a study titled “Distinct Opsin 3 (Opn3) Expression in the Developing Nervous System during Mammalian Embryogenesis.”

Prior research has suggested that individuals living in the northern hemisphere are more likely to develop MS as adults if they were born in the springtime, and less likely if they are born in the autumn. In the southern hemisphere, this is reversed, with those born in the fall more likely to develop MS in adulthood. A 2019 meta-analysis determined that “the month and the season of birth are significantly associated with MS births.”

While the reasons for this are not clear, it’s been proposed that this seasonal difference could be due to the amount of light that a developing baby is exposed to during pregnancy. However, the biological mechanisms that could account for this are not well understood.

Now, researchers have focused on opsins, proteins that are able to sense light, which are heavily expressed by cells in the eye. There, they play a critical role in vision.

For a long time, scientists assumed that these light-sensing proteins were only functional in the eyes. But emerging research suggests that opsins are actually more widely expressed — meaning they have greater activity — in the body’s tissues, implying that these proteins may have functions that are still unknown.

In the new study, a team led by researchers at Umeå University used mice to study how a specific opsin protein, called opsin 3 (OPN3), is expressed throughout early development. To do this, the team engineered mice so that their cells would make OPN3 protein that was attached to a florescent protein, which the researchers could visualize using appropriate imaging tools.

The researchers showed that OPN3 was evident in the mice’s brain structures as early as at 9.5 days of embryonic development. The team also noted OPN3 expression in mice’s developing hearts, pancreases, and intestines.

To learn more, the team then tracked how OPN3 expression in different brain structures changed during development. For example, many brain structures involved in sensation — seeing, smelling, and hearing — produced OPN3 at a relatively early point. Some structures that help to coordinate movement also had OPN3 early on.

As the mice developed, OPN3 production in the nervous system tended to expand. In later embryonic development and after birth, opsin 3 was evident in structures of the forebrain – the front part of the brain that is important for processing information.

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“In this study, evidence is provided that Opn3 is expressed during most of embryonic development,” the researchers concluded, noting that the production of this protein was evident “much earlier than previously reported” in the nervous system.

Since this protein is important for sensing light — specifically, OPN3 is activated by blue light — these results suggest that cells in a developing fetus are able to detect light. And since the protein was present in many critical brain structures in early development, the results imply that it may play a role in regulating the development of these structures, perhaps at least partially through its light-sensing functions.

“Collectively, these results form the basis of further investigations into how Opn3-dependent signaling might regulate the development of the nervous system and other key structures, which might prove significant in understanding the season-of-conception/birth dependent risk of developing” MS and other disorders, the team concluded.

The researchers noted that these findings come from mouse models of MS and that more research is needed to determine if and how they may translate to humans. In addition, the investigators said, “time of birth is only one of several risk factors for the diseases in question.”