Study: Vitamin D Exposure May Increase Development of Dopamine Neurons, Indicating Mechanism of Schizophrenia


Evidence shows vitamin D deficiency is linked to abnormal dopamine signaling disorders in neurodevelopment, including schizophrenia.

Data continue to demonstrate that vitamin D is a differentiation agent for developing dopamine neurons. In a study published in the Journal of Neurochemistry, investigators found that chronic exposure to active vitamin D hormones can increase the capacity of developing dopamine neurons and indicated a better understanding of the mechanisms of developmental vitamin D (DVD) deficiency and schizophrenia.

Nutrition sign vector concept. The power of vitamin D. Chemical formula. Credit: Katsiaryna Hatsak -

Credit: Katsiaryna Hatsak -

Vitamin D has been associated with dopaminergic neurogenesis and differentiation, according to the study, which supports evidence of a link between DVD deficiency and abnormal dopamine signaling disorders based in neurodevelopment, including schizophrenia.

Investigators stated that the results of the study further establish that vitamin D mediates dopaminergic development, including increasing neurite outgrowth, neurite branching, presynaptic protein redistribution, dopamine production, functional releases.

They used in vitro models of varying developing dopaminergic cells, which included human neuroblastoma cells (SH-SY5Y), primary mesencephalic cultures, and mesencephalic/striatal explant co-cultures, according to the study.

The results showed the tyrosine hydroxylase-positive (TH+) SH-SY5Y overexpressing vitamin D receptor cells (VDR+) that were treated with 20 nM of 1,25 dihydroxy vitamin D (1,25OHD) had significantly longer neurites when compared with all-trans-retinoic acid (RA) treatment or vehicle.

Investigators found that even though the same treatment was applied to embryonic day 14.5 (E14.5) mesencephalic, the neurons did not increase in total branching or neurite length. The Sholl analysis also demonstrated an interaction of greater overall neurotic branching, which was produced by 1,25OHD, according to the study.

Additionally, investigators found that cells that had more intense VDR expression produced a greater affect in the presence of 1,25OHD. However, they added that VDR intensity did not correlate with neurite length.

The investigators concluded that 1,25OHD increased the glial-derived growth factor mRNA production in SH-SY5Y/VDR+ cells. Furthermore, when 1,25OHD was added, there was a change in distribution and expression in presynaptic proteins that are involved in synaptic dopamine release.

Treatment with 1,25OHD increased synaptic puncta numbers for both the synaptic makers, according to the investigators. It was previously thought that after the deletion of synaptic vesicle glycoprotein 2C (SV2C), expressed in vesicles of dopaminergic neurons, there was a reduction of synaptic release of dopamine. However, the distribution of presynaptic proteins was not specific to SV2C, according to the study.

The RA treatment had no effect on SV2C, however, 1,25OHD did lead to a reduction of SV2C puncta intensity, which indicates it alters the overall distribution, according to investigators. Importantly, the study authors suggested that 1,25OHD could promote dopamine release indicated from findings on SV2C and extracellular dopamine.

Investigators suggest that 1,25OHD can promote a pharmacological release of dopamine from the TH+ cells. Furthermore, they added that the results suggest that developmental variations of vitamin D could alter dopamine neuron development, adding that the results support that schizophrenia is a developmental dopaminergic disorder.

Further, the results may support new avenues of research around the connection of vitamin D and SV2C functions and its effect on molecular mechanisms of disrupted dopamine-signaling of schizophrenia, the authors concluded.


Pertile RAN, Brigden R, Raman V, Cui X, Du Z, Eyles D. Vitamin D: a potent regulator of dopaminergic neuron differentiation and function. Neurochem. 2023;10.1111/jnc.15829. doi:10.1111/jnc.15829

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