Summary: Neuroscientists discovered how vitamin D deficiency impacts the development of neurons, contributing to disorders such as schizophrenia.

Using innovative technology, they were able to observe that a lack of vitamin D not only changes neuron growth but also affects the brain’s dopamine release mechanism. They found dopamine release was enhanced in cells grown in the presence of vitamin D, compared to a control.

This study underscores the importance of vitamin D in the structural differentiation of dopaminergic neurons and suggests that maternal vitamin D deficiency might alter how early dopaminergic circuits form.

Key Facts:

1.     The research team showed that vitamin D deficiency affects the growth and dopamine release mechanisms in dopaminergic neurons.

2.     They found that dopamine release was enhanced in cells grown in the presence of the vitamin D hormone compared to a control.

3.     The study posits that early alterations to dopamine neuron differentiation due to vitamin D deficiency may be the neurodevelopmental origin of dopamine dysfunction in adults who develop schizophrenia.

Neuroscientists at The University of Queensland have uncovered how vitamin D deficiency affects developing neurons in schizophrenia, using new technology.

The paper was published in the Journal of Neurochemistry.

Professor Darryl Eyles has built on past research out of his laboratory at the Queensland Brain Institute linking maternal vitamin D deficiency and brain development disorders, such as schizophrenia, to understand the functional changes taking place in the brain.

Schizophrenia is associated with many developmental risk factors, both genetic and environmental. While the precise neurological causes of the disorder are unknown, what is known is that schizophrenia is associated with a pronounced change in the way the brain uses dopamine, the neurotransmitter often referred to as the brain’s “reward molecule.”

Professor Eyles has followed the mechanisms that might relate to abnormal dopamine release 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 process of differentiation into early dopaminergic neurons that usually takes place during embryonic development.

They cultured the neurons both in the presence and absence of the active vitamin D hormone. In three different model systems they showed dopamine neurite outgrowth was markedly increased. They then showed alterations in the distribution of presynaptic proteins responsible for dopamine release within these neurites.

“What we found was the altered differentiation process in the presence of vitamin D not only makes the cells grow differently, but recruits machinery to release dopamine differently,” Professor Eyles said.

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

They showed that dopamine release was enhanced in cells grown in the presence of the hormone compared to a control.

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

Leveraging advances in targeting and visualizing single molecules within presynaptic nerve terminals has enabled Professor Eyles and his team to further explore their long-standing belief that maternal vitamin D deficiency changes how early dopaminergic circuits are formed.

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

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

Author: Darryl Eyles
Source: University of Queensland
Contact: Darryl Eyles – University of Queensland
Image: The image is credited to Neuroscience News

Original Research: Open access.
“Vitamin D: A potent regulator of dopaminergic neuron differentiation and function” by Renata Aparecida Nedel Pertile et al. Journal of Neurochemistry

Abstract

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. Consequently, developmental vitamin D (DVD) deficiency has been linked to disorders of abnormal dopamine signaling with a neurodevelopmental basis such as schizophrenia.

Here we provide further evidence of vitamin D’s role as a mediator of dopaminergic development by showing that it increases neurite outgrowth, neurite branching, presynaptic protein re-distribution, dopamine production and functional release in various in vitro models of developing dopaminergic cells including SH-SY5Y cells, primary mesencephalic cultures and mesencephalic/striatal explant co-cultures.

This study continues to establish vitamin D as an important differentiation agent for developing dopamine neurons, and now for the first time shows chronic exposure to the active vitamin D hormone increases the capacity of developing neurons to release dopamine.

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