How Vitamin D deficiency leads to cognitive decline,finds Study

Vitamin D deficiency leads to cognitive decline but its mechanism is not known.Researchers at University of Queensland have found that deficiency of Vitamin D impacts synaptic plasticity which is one of the important neurochemical foundations of learning and memory and in turn leads to cognitive decline.

Over a billion people worldwide are affected by vitamin D deficiency. Although vitamin D deficiency is associated with impaired cognition, the mechanisms mediating this link are poorly understood.

Researchers at University of Queensland have conducted a study to explain why vitamin D is vital for brain health, and how deficiency leads to cognitive decline and disorders including depression and schizophrenia.

Associate Professor Thomas Burne at UQ’s Queensland Brain Institute led the studies, which provide the groundwork for research into better prevention and treatments.

The research is published in Brain Structure and Function and Trends in Neuroscience.

Vitamin D plays various roles in normal brain physiology, including modulating synaptic plasticity.Converging evidence suggests that vitamin D deficiency affects multiple brain processes, including cognitive functioning, in both healthy people and those afflicted with neuropsychiatric illness.

Evidence suggests that vitamin D deficiency impacts synaptic plasticity through a plethora of avenues, including l-type voltage-gated calcium channels and regulation of various neurotransmitters, including NO.synaptic plasticity is the ability of synapses to strengthen or weaken over time, in response to increases or decreases in their activity and is one of the important neurochemical foundations of learning and memory .

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The extracellular matrix (ECM) has now emerged as an important participant of synaptic plasticity and a new hypothesis is that vitamin D may interact with aggregates of the ECM, perineuronal nets (PNNs), to regulate brain plasticity. An emerging concept is that vitamin D deficiency may weaken the integrity of perineuronal nets,PNNs,which play essential roles in cognitive processes such as learning and memory. Dysregulation of PNNs is likely to disturb neural-circuit function and impair cognitive functioning.

“Over a billion people worldwide are affected by vitamin D deficiency, and there is a well-established link between vitamin D deficiency and impaired cognition,” Dr Burne said.

“Unfortunately, exactly how vitamin D influences brain structure and function is not well understood, so it has remained unclear why deficiency causes problems.”

Dr Burne’s team found that vitamin D levels affect a type of ‘scaffolding’ in the brain, called perineuronal nets.

“These nets form a strong, supportive mesh around certain neurons, and in doing so they stabilise the contacts these cells make with other neurons,” he said.

Researchers removed vitamin D from the diet of a group of healthy adult mice, and after 20 weeks found a significant decline in their ability to remember and learn compared to a control group.

Dr Burne said the vitamin D deficient group had a pronounced reduction in perineuronal nets in the hippocampus, the brain region crucial to memory formation.

“There was also a stark reduction in both the number and strength of connections between neurons in that region.”

Dr Burne’s team propose that vitamin D plays an important role in keeping perineuronal nets stable, and that when vitamin D levels drop, this ‘scaffolding’ is more easily degraded by enzymes.

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

Associate Professor Burne said the hippocampus may be most strongly affected by vitamin D deficiency because it is much more active than other brain regions.

“It’s like the canary in the coalmine—it might fail first because its high energy requirement makes it more sensitive to the depletion of essential nutrients like vitamin D.

“Intriguingly, the right side of the hippocampus was more affected by vitamin D deficiency than the left side.”

Associate Professor Burne said loss of function in this area could be an important contributor to the hallmarks of schizophrenia, including severe memory deficits and a distorted perception of reality.

“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.”