Why A Lack Of Vitamin D Is So Bad For The Brain

Perineuronal nets (bright green) surround particular neurons (blue). The nets help neurons form the connections they need, but without sufficient vitamin D, they are weakened in the hippocampus. Phoebe Mayne, UQ

If you want to convince your boss to send you somewhere warm in winter, we may have the answer if you promise to sunbathe. Lack of vitamin D, caused by insufficient exposure to sunlight, can affect the brain in many ways, none of them likely to improve your work performance. Even among relatively healthy older people, vitamin D deficiency has been linked to reduced memory and cognition. Meanwhile, evidence for an association with mental illness, particularly schizophrenia, keeps growing. Now, neuroscientists may have found a likely mechanism.

When Dr Thomas Burne of the University of Queensland deprived healthy adult rats of vitamin D, their perineuronal nets were affected – declining by as much as half in the essential hippocampus region.

These nets have been compared to scaffolding for the brain. They stabilize important neurons and the connections between them; researchers have observed fewer and weaker connections between neurons that lost their nets. In papers published in Brain Structure and Function and Trends in Neuroscience, Burne and colleagues concluded that vitamin D may offer protection against enzymes that cut into the scaffolding.

Burne told IFLScience that perineuronal nets are not always beneficial – in some parts of the brain, they appear to inhibit new learning, and their removal there has been shown to benefit Alzheimer's sufferers. However, in the hippocampus, where the net loss was focused, strong scaffolding appears crucial to memory formation. Certainly, Burne's deficient mice were less able to learn than counterparts with adequate vitamin D and intact nets.

The most surprising part of the study was that the right side of the rats' hippocampus was more affected than the left. Why this might be is unclear, but Burne told IFLScience, “the right hippocampus is very important for perceptions of reality,” which may explain long-standing work Burne has been a part of that links low vitamin D before birth to schizophrenia. 

Of all the molecules necessary for good health, vitamin D seems an unlikely candidate for widespread deficiency. Most of the world can get an adequate dose by spending time outdoors with skin uncovered each day, many foods are rich sources, and supplements are cheap. Yet Burne said in a statement: “Over a billion people worldwide are affected by vitamin D deficiency.”

Burne is part of a team that has produced many papers linking vitamin D to brain health. He told IFLScience, the relationship is complicated. “If you take anyone with almost any disease, they will generally have lower vitamin D than healthy controls,” Burne said. “So it looks like deficiency is a consequence of getting ill.” Nevertheless, for some conditions, such as cognitive decline among the elderly, we have reason to believe a shortage of vitamin D is a cause as well as an effect.

Burne acknowledged that the work leaves many questions unanswered. The team have theories on why vitamin D is necessary for strong scaffolds, and ideas about how to test them, but as yet they have no confirmation. Burne also told IFLScience that so many roles have been found for vitamin D in the brain, it is likely that weak scaffolding is just one of many ways its absence is felt (and theories about others remain untested).

The researchers hope, however, that the publication of a mechanism will address the fact that vitamin D is promoted for bone health and cancer prevention, but rarely for the brain.

“We are also particularly excited to have discovered these nets can change in adult mice,” Burne said. “I’m hoping that because they’re dynamic there is a chance that we can rebuild them, and that could set the stage for new treatments.”

 

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