Findings from other research indicated that developmental vitamin D deficiency has been correlated with disorders of abnormal dopamine (DA) signaling with a neurodevelopmental basis, such as schizophrenia.

In a publication in the Journal of Neurochemistry, neuroscientists from the Queensland Brain Institute used novel technology to understand how vitamin D deficiency affects the development of neurons in schizophrenia.

Lead researcher Darryl Eyles, professor at the Queensland Brain Institute, and colleagues expanded on past research connecting maternal vitamin D deficiency and brain development disorders, such as schizophrenia, to understand the functional variations that transpire in the brain.

In the research, Dr. Eyles pursued the mechanisms that might relate to abnormal DA release and discovered that maternal vitamin D deficiency affects the early development and later differentiation of dopaminergic neurons.

For this study, the researchers created DA-like cells to replicate the process of differentiation into early dopaminergic neurons that generally transpire during embryonic development. The researchers cultured the neurons both in the presence and absence of the active vitamin D hormone. In three different model systems, they demonstrated that DA neurite outgrowth was significantly expanded. Additionally, they demonstrated alterations in the distribution of presynaptic proteins responsible for DA release within these neurites.

In a press release on the Queensland Brain Institute website, Dr. Eyles stated, “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.”

Utilizing a new visualization tool recognized as false fluorescent neurotransmitters, the team could then examine the functional variations in presynaptic DA uptake and release in the presence and absence of vitamin D. The researchers demonstrated that DA release was enhanced in cells grown in the presence of the hormone compared with a control.

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

Based on their findings, the authors wrote, “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 [developmental vitamin D] deficiency and schizophrenia.”

The authors also noted, “Our results also suggest possible new avenues of research aimed at investigating the connection between vitamin D and SV2C [synaptic vesicle glycoprotein 2C] function with respect to the molecular mechanisms underlying the disrupted DA-signaling found in schizophrenia.”

The researchers are investigating whether other environmental risk factors for schizophrenia, such as maternal hypoxia or infection, equally modify the trajectory of DA neuron differentiation.

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

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