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Vitamin D Deficiency Weakens Brain Scaffolding

February 27, 2019

Removing vitamin D from the diet of healthy adult mice caused a significant drop in their ability to remember and learn, which researchers said was due to a pronounced reduction in perineuronal nets in the hippocampus.

The findings, published online in Trends in Neurosciences, may explain why vitamin D is vital for brain health and how deficiency can lead to schizophrenia and depression.

Perineuronal nets
Perineuronal nets (green) surround particular neurons (blue). Fluorescence labelling shows the detail of the structures. Photo courtesy Phoebe Mayne, University of Queensland

“These [perineuronal] nets form a strong, supportive mesh around certain neurons, and in doing so they stabilize the contacts these cells make with other neurons,” said researcher Thomas Burne, PhD, an associate professor in the brain institute at the University of Queensland in Australia.

“As neurons in the hippocampus lose their supportive perineuronal nets,” he added, “they have trouble maintaining connections, and this ultimately leads to a loss of cognitive function.”

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Dr. Burne and Phoebe Mayne, a PhD student, reached their finding after removing vitamin D from the diet of healthy adult mice. Within 20 weeks, researchers noted a significant decline in cognitive functioning in the mice, compared with mice that continued to receive vitamin D in their diet. The mice deficient in vitamin D had a pronounced reduction in perineuronal nets in the hippocampus, the brain region essential for memory formation, according to the study.

“There was also a stark reduction in both the number and strength of connections between neurons in that region,” said Dr. Burne, who proposed that vitamin D is crucial for keeping perineuronal nets stable. When levels of vitamin D decrease, he explained, nets are more easily degraded by enzymes.

In the mice, vitamin D deficiency affected the right side of the hippocampus more than the left side, the study found.

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Loss of function in the area, Dr. Burne said, could be an important contributor to the severe memory deficits and distorted perception of reality associated with schizophrenia.

“The next step is to test this new hypothesis on the link between vitamin D deficiency, perineuronal nets, and cognition,” he said.

“We are also particularly excited to have discovered these nets can change in adult mice. 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.”

—Jolynn Tumolo


Mayne PE, Burne THJ. Vitamin D in synaptic plasticity, cognitive function, and neuropsychiatric illness. Trends in Neurosciences. 2019 February 19;[Epub ahead of print].

Potential link between vitamin D deficiency and loss of brain plasticity [press release]. Brisbane, Australia: University of Queensland; February 20, 2019.

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