Critical role of vitamin D in dopaminergic function and schizophrenia

summary: Neuroscientists have discovered how vitamin D deficiency affects the development of neurons, contributing to disorders such as schizophrenia.

Using innovative technology, they were able to observe that vitamin D deficiency not only alters the development of neurons, but also affects the dopamine release mechanism in the brain. They found that dopamine release was improved in cells cultured in the presence of vitamin D, compared to a control.

This study confirms the importance of vitamin D in the structural differentiation of dopaminergic neurons and suggests that maternal vitamin D deficiency may alter how early dopamine circuits are formed.

Key facts:

1. The research team showed that vitamin D deficiency affects the mechanisms of growth and dopamine secretion in dopamine neurons.
2. They found that dopamine release was improved in cells cultured in the presence of the vitamin D hormone, compared to a control.
3. The study hypothesizes that early changes in dopaminergic neuron differentiation due to vitamin D deficiency may be the neurodevelopmental origin of dopamine dysfunction in adults who develop schizophrenia.

source: University of Queensland

Neuroscientists at the University of Queensland have discovered how vitamin D deficiency affects developing neurons in schizophrenia using a new technique.

The paper was published in Journal of Neurochemistry.

Professor Darrell Iles built on previous research outside his lab at the Queensland Brain Institute linking maternal vitamin D deficiency to disorders of brain development, such as schizophrenia, to understand the functional changes that occur in the brain.

Schizophrenia is associated with many developmental risk factors, both genetic and environmental. While the exact neurological causes of the disorder are not known, what is known is that schizophrenia is associated with a distinct change in the way the brain uses dopamine, the neurotransmitter often referred to as the brain’s “reward molecule.”

Professor Ailes pursued mechanisms that might relate to abnormal dopamine secretion and discovered that maternal vitamin D deficiency affects the early development and later differentiation of dopaminergic neurons.

The team at the Queensland Brain Institute developed dopamine-like cells to replicate the differentiation process in early dopaminergic neurons that normally occurs during embryonic development.

They transplanted neurons in both the presence and absence of the active vitamin D hormone. In three different model regimens, they were shown to significantly increase dopaminergic neurite outgrowth. They then showed changes in the distribution of presynaptic proteins responsible for dopamine release within these neurons.

“What we found is that the altered differentiation process in the presence of vitamin D not only causes cells to grow differently, but also recruits a mechanism to release dopamine differently,” said Professor Iles.

Using a new visualization tool known as pseudofluorescent neurotransmitters, the team can then analyze functional changes in presynaptic dopamine uptake and release in the presence and absence of vitamin D.

They showed that dopamine secretion was improved in cells cultured in the presence of the hormone compared to a control.

“This is definitive evidence that vitamin D affects the structural differentiation of dopaminergic neurons.”

Taking advantage of advances in targeting and visualizing single molecules within the terminals of presynaptic nerves has enabled Professor Iles and his team to explore their long-held belief that maternal vitamin D deficiency alters how early dopamine circuits are formed.

The team is now exploring whether other environmental risk factors for schizophrenia, such as maternal hypoxia or infection, similarly alter the differentiation pathway of dopamine neurons.

Iles and his team believe that such early changes in dopamine neuron differentiation and function may be the neurodevelopmental origin of dopamine dysfunction later in adults who develop schizophrenia.

About this neuroscience and mental health research news

author: Daryl Isles
source: University of Queensland
communication: Darrell Isles – University of Queensland
picture: Image credited to Neuroscience News

Original search: open access.
“Vitamin D: a potent regulator of dopaminergic neuron differentiation and functionBy Renata Aparecida, Nedel Bertil et al. Journal of Neurochemistry

a summary

Vitamin D: a potent regulator of dopaminergic neuron differentiation and function

Vitamin D has been identified as a key factor in dopaminergic neurogenesis and differentiation. Thus, developmental vitamin D deficiency (DVD) has been linked to abnormal dopamine signaling disorders with a neurodevelopmental basis such as schizophrenia.

Here we provide further evidence for a role for vitamin D as a mediator of dopaminergic development by showing that it increases neurite outgrowth, neurite branching, presynaptic protein redistribution, dopamine production and functional secretion in various in vitro models of dopaminergic cell development including SH-SY5Y Cells, mesencephalic primary cultures and mesencephalic co-agro/striatum.

This study continues to identify vitamin D as a differentiation factor important for developing dopamine neurons, and now shows for the first time that chronic exposure to the active hormone vitamin D increases the ability of developing neurons to release dopamine.

This study also has implications for understanding the mechanisms underlying the link between DVD deficiency and schizophrenia.