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 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. 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.

Prenatal hypoxia alters the early ontogeny of dopamine neurons.

Dopaminergic (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. Pregnant mice were exposed to a hypoxic environment of 10% oxygen for 48 h from embryonic day 10 (E10) to E12. Embryonic brains were collected and the positioning of mesencephalic cells, expression of DA specification and maturation factors were examined along with the expression of factors that may govern the migration of these neurons. We show that prenatal hypoxia results in a decrease in dopaminergic progenitors retards early DA neuron lateral migration and reduces expression of the receptors known to govern this process. A second time-point, postnatal day 10 (P10) was also examined in order to assess whether prenatal hypoxia alters early presynaptic architecture in the developing striatum. We show reduced expression of tyrosine hydroxylase (TH) in the postnatal striatum along with increases in the density of high-probability DA release sites within TH varicosities. These findings add to the emerging literature showing that multiple epidemiologically validated environmental risk factors for schizophrenia may induce early alterations to develop DA systems. This may represent a possible convergent mechanism in the onset of presynaptic DA dysfunction in patients.

Developmental vitamin D deficiency increases foetal exposure to testosterone.

BACKGROUND: 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. Epidemiological studies have identified several environmental risk factors associated with ASD, including developmental vitamin D (DVD) deficiency. We have demonstrated in an animal model that DVD-deficiency is associated with a hyper-inflammatory response in placentas from male but not female foetuses. Vitamin D also regulates the expression of several steroidogenic enzymes in vitro. Therefore using this animal model, we have examined whether DVD-deficiency leads to increased sex-steroid levels in both the maternal and foetal compartments. METHODS: Female rats are fed a vitamin D deficient diet from 6 weeks before mating until tissue collection at embryonic day 18. We examined the levels of testosterone, androstenedione and corticosterone in maternal plasma, foetal brains and amniotic fluid. We further examined gene expressions of steroidogenic enzymes and DNA methylation of aromatase promoters in foetal brains as a potential molecular mechanism regulating testosterone expression. RESULTS: We show that DVD-deficiency increases testosterone levels in maternal blood. We also show elevated levels of testosterone and androstenedione in the amniotic fluid of female but not male DVD-deficient foetuses. Testosterone levels were also elevated in DVD-deficient male brains. Vitamin D, like other steroid-related hormones, regulates gene expression via methylation. Therefore we examined whether the significant elevation in testosterone in male brains was due to such a potential gene-silencing mechanism. We show that the promoter of aromatase was hyper-methylated compared to male controls. LIMITATIONS: A reduction in aromatase, in addition to causing excessive testosterone, could also lead to a reduction in estradiol which was not examined here. CONCLUSIONS: This study is the first to show how an epidemiologically established environmental risk factor for ASD may selectively elevate testosterone in male embryonic brains. These findings provide further mechanistic support for the prenatal sex steroid theory of ASD.

Melatoninergic System in Parkinson's Disease: From Neuroprotection to the Management of Motor and Nonmotor Symptoms.

Melatonin 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 α-synuclein aggregation, thus protecting the dopaminergic system against damage. The unbalance of pineal melatonin synthesis can predispose the organism to inflammatory and neurodegenerative diseases such as Parkinson's disease (PD). The aim of this review is to summarize the knowledge about the potential role of the melatoninergic system in the pathogenesis and treatment of PD. The literature reviewed here indicates that PD is associated with impaired brain expression of melatonin and its receptors MT1 and MT2. Exogenous melatonin treatment presented an outstanding neuroprotective effect in animal models of PD induced by different toxins, such as 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), rotenone, paraquat, and maneb. Despite the neuroprotective effects and the improvement of motor impairments, melatonin also presents the potential to improve nonmotor symptoms commonly experienced by PD patients such as sleep and anxiety disorders, depression, and memory dysfunction.

Bacterial cellulose production by Gluconacetobacter xylinus by employing alternative culture media.

Bacterial cellulose (BC) is used in different fields as a biological material due to its unique properties. Despite there being many BC applications, there still remain many problems associated with bioprocess technology, such as increasing productivity and decreasing production cost. New technologies that use waste from the food industry as raw materials for culture media promote economic advantages because they reduce environmental pollution and stimulate new research for science sustainability. For this reason, BC production requires optimized conditions to increase its application. The main objective of this study was to evaluate BC production by Gluconacetobacter xylinus using industry waste, namely, rotten fruits and milk whey, as culture media. Furthermore, the structure of BC produced at different conditions was also determined. The culture media employed in this study were composed of rotten fruit collected from the disposal of free markets, milk whey from a local industrial disposal, and their combination, and Hestrin and Schramm media was used as standard culture media. Although all culture media studied produced BC, the highest BC yield-60 mg/mL-was achieved with the rotten fruit culture. Thus, the results showed that rotten fruit can be used for BC production. This culture media can be considered as a profitable alternative to generate high-value products. In addition, it combines environmental concern with sustainable processes that can promote also the reduction of production cost.