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 signalling 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.
View Article and Find Full Text PDFDopaminergic (DA) dysfunction is a significant feature in the pathophysiology of schizophrenia. Established developmental risk factors for schizophrenia such as maternal immune activation (MIA) or developmental vitamin D (DVD) deficiency, when modelled in animals, reveal the differentiation of early DA neurons in foetal brains is delayed suggesting this may be a convergent aetiological pathway. Here we have assessed the effects of prenatal hypoxia, another well-known developmental risk factor for schizophrenia, on developing DA systems.
View Article and Find Full Text PDFSchizophrenia is a neurodevelopmental disorder associated with abnormal dopamine (DA) signalling and disruptions in early brain development. We have shown that developmental vitamin D-deficiency (DVD-deficiency) increases the risk of schizophrenia in offspring and impairs various aspects of brain development in rodents, particularly that of DA neurons, however the molecular basis of these impairments remains unclear. Here, we explore whether small non-coding microRNAs (miRNAs) are involved.
View Article and Find Full Text PDFBackground: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders which are more common in males. The 'prenatal sex steroid' hypothesis links excessive sex-steroid exposure during foetal life with the behavioural differences observed in ASD. However, the reason why sex steroid exposure may be excessive remains unclear.
View Article and Find Full Text PDFMelatonin is synthesized by several tissues besides the pineal gland, and beyond its regulatory effects in light-dark cycle, melatonin is a hormone with neuroprotective, anti-inflammatory, and antioxidant properties. Melatonin acts as a free-radical scavenger, reducing reactive species and improving mitochondrial homeostasis. Melatonin also regulates the expression of neurotrophins that are involved in the survival of dopaminergic neurons and reduces -synuclein aggregation, thus protecting the dopaminergic system against damage.
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