Darryl W Eyles

University of Queensland, Brisbane, Queensland, Australia

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Publications (180)553.3 Total impact

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    ABSTRACT: Background/Objectives: Maternal vitamin D deficiency during pregnancy may influence offspring kidney health. We aimed to examine the associations of 25-hydroxyvitamin D (25(OH)D) blood levels during fetal life with kidney outcomes at school age. Subjects/Methods: This study was embedded in a population-based prospective cohort study among 4212 mother–child pairs. We measured maternal second trimester (18–25 weeks) and fetal cord blood (at birth) 25(OH)D levels. At a median age of 6.0 years, we measured children’s combined kidney volume, glomerular filtration rate (eGFR) from creatinine and cystatin C serum levels, and microalbuminuria from albumin and creatinine urine levels. Results: Of all mothers, 21.9% had severely deficient levels (25(OH)D <25.0 nmol/l), 25.7% had deficient levels (25.0–49.9 nmol/l), 25% had sufficient levels (50.0–74.9 nmol/l) and 27.4% had optimal levels (greater than or equal to75.0 nmol/l). Maternal 25(OH)D levels were not consistently associated with childhood combined kidney volume. Higher maternal 25(OH)D levels were associated with lower childhood eGFR (difference −0.94 ml/min per 1.73 m2 (95% confidence interval, −1.73; −0.15) per 1 standard deviation (s.d.) increase in 25(OH)D). Maternal 25(OH)D levels were not associated with microalbuminuria. Cord blood 25(OH)D levels were not associated with childhood kidney outcomes. The associations of maternal 25(OH)D levels with childhood eGFR were partly explained by childhood vitamin D status. Conclusions: Our findings suggest that maternal 25(OH)D levels during pregnancy may influence childhood kidney outcomes. These results should be considered hypothesis generating. Further studies are needed to replicate the observations, to examine the underlying mechanisms and to identify the long-term clinical consequences.
    No preview · Article · Dec 2015 · European Journal of Clinical Nutrition
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    ABSTRACT: Background: Exposure to low levels of vitamin D in fetal life might affect the developing immune system, and subsequently the risk of childhood eczema. We examined whether 25-hydroxyvitamin D levels in mid-gestation and at birth were associated with the risk of eczema until the age of 4 years. Methods: In a population-based prospective cohort study of 3,019 mothers and their children, maternal blood samples in mid-gestation and umbilical cord blood samples at birth were used to determine 25-hydroxyvitamin D levels (severely deficient <25.0 nmol/L, deficient 25.0-49.9 nmol/L, sufficient 50.0-74.9 nmol/L, optimal ≥75.0 nmol/L). Eczema was prospectively assessed by annual questionnaires until the age of 4 years. Eczema patterns included never, early (age ≤1 year only), late (age >1 year only), and persistent eczema (age ≤ and >1 year). Data were assessed using generalized estimating equations and multinomial regression models. Results: Compared with the optimal 25-hydroxyvitamin D group, sufficient, deficient and severely deficient groups of 25-hydroxyvitamin D level in mid-gestation were not associated with the risk of overall eczema (odds ratios (95%confidence interval): 1.09 (0.82, 1.43), 1.04 (0.87, 1.25) and 0.94 (0.81, 1.10), p-values for trend >0.05), nor with eczema per year or eczema patterns in children up to the age of 4 years. Similarly, we observed no associations of 25-hydroxyvitamin D groups at birth with any eczema outcome. Conclusion: Our results suggest that levels of 25-hydroxyvitamin D in mid-gestation and at birth are not associated with the risk of overall eczema, eczema per year or eczema patterns among children until the age of 4 years. This article is protected by copyright. All rights reserved.
    No preview · Article · Dec 2015 · Pediatric Allergy and Immunology
  • Emilia M Lefevre · Darryl W Eyles · Thomas H.J. Burne
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    ABSTRACT: The pathophysiology of schizophrenia is associated with disturbed glutamate signalling, particularly via a dysfunction of the N-methyl-D-aspartate (NMDA) receptor. In rodents, behavioural sensitisation to the NMDA receptor antagonist MK-801 is proposed to recapitulate aspects of the NMDA receptor hypofunction hypothesis of schizophrenia. The aim of this study was to determine the modulatory role of MK-801 dose and environmental context on the development and expression of MK-801-induced behavioural sensitisation. Sprague Dawley rats were administered saline or varying doses of MK-801 (i.p.) once daily for 7 days and locomotor activity was recorded. After 5 days of withdrawal, rats were challenged with their respective dose to test for sensitisation. From this experiment a sensitizing dose was obtained. In the second experiment the magnitude of sensitisation was compared between rats that were treated in either a home or test environmental context. Rats treated with 0.25mg/kg MK-801 developed robust sensitisation when challenged after withdrawal. Rats treated with lower (0.1mg/kg) or higher (0.5mg/kg) doses of MK-801 did not develop locomotor sensitisation. Sensitisation to 0.25mg/kg MK-801 developed equally between rats treated in the home or test context. The study shows that male Sprague Dawley rats develop behavioural sensitisation to repeated injections of MK-801. The development of sensitisation is selective to MK-801 dose in an inverted-U dose response fashion. In this paradigm MK-801 induced sensitisation was expressed similarly between groups treated in two distinct environmental contexts.
    No preview · Article · Nov 2015 · Behavioural brain research
  • Kathie Overeem · DW Eyles · JJ McGrath · THJ Burne
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    ABSTRACT: Vitamin D deficiency has been proposed as an environmental risk factor for several neurological disorders. To investigate the biological plausibility of this risk factor, vitamin D (DVD) deficiency rodent models have been used to examine the impact of DVD deficiency on neurobiology and behaviour. The majority of these studies have taken a developmental stance and examined the impact of vitamin D deficiency during gestation on the adult behaviour of the offspring. In the rat, the most constant behavioural phenotypes include hyperlocomotion in response to novelty, psychostimulant sensitively, impulsivity, and augmented motivation. However, in the mouse increased exploratory behaviour and motivational alterations are observed. Researchers have also examined the affect of adult vitamin D deficiency in rodents. The resultant behavioural alterations include increased exploratory activity and impulsivity in the rat, while increased hyperlocomotion and sensory sensitivity is observed in the mouse. Thus, both the developing and adult brain are sensitive to dietary vitamin D status. However, the behavioural alterations are subtle and influenced by factors such as species, strain, sex, and age. This illustrates the amenability and complexity of neurobiological systems that are influenced by vitamin D status. Nonetheless, with increasing evidence for epidemiological associations between neuropathological disorders and vitamin D, carefully designed rodent models are well placed as a tool to explore the neurobiological and behavioural domains that may be sensitive to vitamin D.
    No preview · Article · Nov 2015
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    ABSTRACT: Background: Population-based studies have confirmed that the prevalence of vitamin D deficiency is substantial in many societies, and is of particular concern in pregnant women. Vitamin D deficiency during pregnancy is associated with a wide range of adverse maternal and offspring health outcomes. To date, studies of vitamin D deficiency during pregnancy have focused on measurements at one or two time points in isolation. We examined both midgestation and cord blood 25 hydroxyvitamin D (25OHD) concentration and explored the prevalence and correlates of vitamin D deficiency in a large ethnically diverse cohort of pregnant women and their infants in the Netherlands. Methods: This study was embedded in the Generation R Study, a population-based prospective cohort from fetal life onwards in Rotterdam, The Netherlands. Using a highly sensitive tandem mass spectroscopy-based assay, we measured 25OHD in 7256 midgestation samples (mean gestation 20.6 weeks) and 5023 neonatal cord blood samples (mean gestation 40.0 weeks). Using a conservative threshold of less than 25 nmol/L to define vitamin D deficiency, we examined the prevalence and socio-demographic correlates of vitamin D deficiency in mothers and infants. We also derived a measure of vitamin D deficiency based on the two time points in order to explore persistent vitamin D deficiency in mother-infant pairs. Results: The prevalence of vitamin D deficiency at midgestation was 26%, while in neonates 46% were deficient. 21% of the mother-infant pairs had persistent vitamin D deficiency (i.e. deficient in maternal and cord samples) and an additional 29% were vitamin D deficient in one of the two samples only. Persistent vitamin D deficiency was strongly associated with non-European ancestry and spring birth. Conclusions: A sizeable proportion of women and their neonatal offspring in the Generation R cohort were vitamin D deficient. In light of the large body of evidence linking vitamin D deficiency with adverse health outcomes for pregnant women and their offspring, our findings indicate a large unmet need in this population. In particular, women and infants from non-European ethnic background are at high risk of vitamin D deficiency.
    No preview · Article · Sep 2015 · The Journal of steroid biochemistry and molecular biology
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    ABSTRACT: Background: Exposure to low levels of vitamin D in fetal life might be a risk factor for childhood asthma. Objective: We examined whether 25-hydroxyvitamin D levels in mid-gestation and at birth were associated with higher airway resistance and inflammation, and increased risks of wheezing and asthma in school-age children. Methods: We performed a population-based prospective cohort study among 3,130 mothers and their children. Maternal blood samples in mid-gestation and umbilical cord blood samples at birth were used to determine 25-hydroxy vitamin D levels. At age 6 years, airway resistance (Rint) was measured by interrupter technique and airway inflammation by Fractional exhaled Nitric Oxide (FENO) using NIOX chemiluminescence analyzer. Wheezing and asthma were prospectively assessed by annual questionnaires until age 6 years. Results: Maternal levels of 25-hydroxy vitamin D in mid-gestation were not associated with Rint, FeNO, wheezing patterns or asthma. Children in thelowest tertile of 25-hydroxy vitamin D levels at birth had a higher Rint (Z-score (95% Confidence Interval[95% CI]): -0.42 (-0.84, -0.01), p-value for trend<0.05), compared to those in the highest tertile group. The effect estimate attenuated when child's current 25-hydroxy vitamin D level was taken into account (Z-score (95% CI): -0.55 (-1.08, 0.01)). Conclusion and clinical relevance: Low levels of 25-hydroxy vitamin D at birth were associated with a higher airway resistance in childhood. Additional adjustment for child's current 25-hydroxy vitamin D level reduced the effect size of the association. Further studies are needed to replicate these findings and to examine mechanisms underlying the observed association, and the long-term consequences. This article is protected by copyright. All rights reserved.
    No preview · Article · Sep 2015 · Clinical & Experimental Allergy
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    Xiaoying Cui · Renata Pertile · Peiyun Liu · Darryl W Eyles
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    ABSTRACT: Vitamin D is a neuroactive steroid. Its genomic actions are mediated via the active form of vitamin D, 1,25(OH)2D3, binding to the vitamin D receptor (VDR). The VDR emerges in rat mesencephalon at embryonic day 12, representing the peak period of dopaminergic cell birth. Our prior studies reveal that developmental vitamin D (DVD)-deficiency alters the ontogeny of dopaminergic neurons in the developing mesencephalon. There is also consistent evidence from others that 1,25(OH)2D3 promotes the survival of dopaminergic neurons in models of dopaminergic toxicity. In both developmental and toxicological studies it has been proposed that 1,25(OH)2D3 may modulate the differentiation and maturation of dopaminergic neurons; however, to date there is lack of direct evidence. The aim of the current study is to investigate this both in vitro using a human SH-SY5Y cell line transfected with rodent VDR and in vivo using a DVD-deficient model. Here we show that in VDR-expressing SH-SY5Y cells, 1,25(OH)2D3 significantly increased production of tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine synthesis. This effect was dose- and time-dependent, but was not due to an increase in TH-positive cell number, nor was it due to the production of trophic survival factors for dopamine neurons such as glial derived neurotrophic factor (GDNF). In accordance with 1,25(OH)2D3's anti-proliferative actions in the brain, 1,25(OH)2D3 reduced the percentage of dividing cells from approximately 15% to 10%. Given the recently reported role of N-cadherin in the direct differentiation of dopaminergic neurons, we examined here whether it may be elevated by 1,25(OH)2D3. We confirmed this in vitro and more importantly, we showed DVD-deficiency decreases N-cadherin expression in the embryonic mesencephalon. In summary, in our in vitro model we have shown 1,25(OH)2D3 increases TH expression, decreases proliferation and elevates N-cadherin, a potential factor that mediates these processes. Accordingly all of these findings are reversed in the developing brain in our DVD-deficiency model. Remarkably our findings in the DVD-deficiency model phenocopy those found in a recent model where N-cadherin was regionally ablated from the mesencephalon. This study has, for the first time, shown that vitamin D directly modulates TH expression and strongly suggests N-cadherin may be a plausible mediator of this process both in vitro and in vivo. Our findings may help to explain epidemiological data linking DVD deficiency with schizophrenia. Copyright © 2015. Published by Elsevier Ltd.
    Full-text · Article · Jul 2015 · Neuroscience
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    ABSTRACT: Wolbachia are endosymbionts that infect approximately 40% of all insect species and are best known for their ability to manipulate host reproductive systems. Though the effect Wolbachia infection has on somatic tissues is less well understood, when present in cells of the adult Drosophila melanogaster brain, it exerts an influence over behaviors related to olfaction. Here we show that a strain of Wolbachia influences male aggression in flies, which is critically important in mate competition. A specific strain of Wolbachia was observed to reduce the initiation of aggressive encounters in Drosophila males when compared against their uninfected controls. To determine how Wolbachia was able to alter aggressive behavior, we investigated the role of octopamine, a neurotransmitter known to influence male aggressive behavior in many insect species. Transcriptional analysis of the octopamine biosynthesis pathway revealed that two essential genes, tryrosine decarboxylase and tyramine β-hydroxylase, were significantly down regulated in Wolbachia infected flies. Quantitative chemical analysis also showed that total octopamine levels were significantly reduced in the adult heads. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    Full-text · Article · May 2015 · Applied and Environmental Microbiology
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    ABSTRACT: Insufficient vitamin D activity has attracted increasing interest as a possible underlying risk factor in disorders of the central nervous system, including autism. In this study, 25-hydroxyvitamin D (25(OH)D) was analysed in 58 Sweden-born sibling pairs, in which one child had autism spectrum disorder (ASD) and the other did not. The study group consisted of two representative samples; 47 Gothenburg sibling pairs with mixed ethnicities and 11 Stockholm sibling pairs with Somali background. 25(OH)D levels were analysed in the stored dried blood spots taken in the neonatal period for metabolic screening. The collapsed group of children with ASD had significantly lower vitamin D levels (M = 24.0 nM, SD = 19.6) as compared with their siblings (M = 31.9 nM, SD = 27.7), according to a paired samples t-test (P = 0.013). The difference was - most likely - not only accounted for by a difference in season of birth between ASD and non-ASD siblings since the mean 25(OH)D levels differed with similar effect size between the sibling pairs born during winter and summer, respectively. All children with African/Middle East background, both the children with ASD and their non-ASD siblings, had vitamin D deficiency. The findings suggest that low prenatal vitamin D may act as a risk factor for ASD, however, there is a need for replication with larger samples. Future research should study whether or not adequate supplementation of vitamin D to pregnant women might lower the risk for ASD in the offspring.
    Full-text · Article · Jan 2015 · Molecular Autism
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    ABSTRACT: Cytokines and vitamin D both have a role in modulating the immune system, and are also potentially useful biomarkers in mental illnesses such as major depressive disorder (MDD) and schizophrenia. Studying the variability of cytokines and vitamin D in a healthy population sample may add to understanding the association between these biomarkers and mental illness. To assess genetic and environmental contributions to variation in circulating levels of cytokines and vitamin D (25-hydroxy vitamin D: 25(OH)D3), we analyzed data from a healthy adolescent twin cohort (mean age 16.2 years; standard deviation 0.25). Plasma cytokine measures were available for 400 individuals (85 MZ, 115 DZ pairs), dried blood spot sample vitamin D measures were available for 378 individuals (70 MZ, 118 DZ pairs). Heritability estimates were moderate but significant for the cytokines transforming growth factor-β1 (TGF-β1), 0.57 (95% CI 0.26-0.80) and tumor necrosis factor-receptor type 1 (TNFR1), 0.50 (95% CI 0.11-0.63) respectively. Measures of 25(OH)D3 were within normal range and heritability was estimated to be high (0.86, 95% CI 0.61-0.94). Assays of other cytokines did not generate meaningful results. These potential biomarkers may be useful in mental illness, with further research warranted in larger sample sizes. They may be particularly important in adolescents with mental illness where diagnostic uncertainty poses a significant clinical challenge.
    Full-text · Article · Dec 2014 · Twin Research and Human Genetics
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    ABSTRACT: Viruses are frequently associated with acute exacerbations of asthma, but the extent to which they contribute to the level of day-to-day symptom control is less clear. We sought to explore the relationship between viral infections, host and environmental factors, and respiratory symptoms in children. Sixty-seven asthmatic children collected samples twice weekly for an average of 10 weeks. These included nasal wash fluid and exhaled breath for PCR-based detection of viral RNA, lung function measurements, and records of medication use and asthma and respiratory symptoms in the previous 3 days. Atopy, mite allergen exposure, and vitamin D levels were also measured. Mixed-model regression analyses were performed. Human rhinoviruses (hRVs) were detected in 25.5% of 1232 nasal samples and 11.5% of breath samples. Non-hRV viruses were detected in less than 3% of samples. hRV in nasal samples was associated with asthma symptoms (cough and phlegm: odds ratio = 2.0; 95% CI = 1.4-2.86, P = .0001; wheeze and chest tightness: odds ratio = 2.34, 95% CI = 1.55-3.52, P < .0001) and with cold symptoms, as reported concurrently with sampling and 3 to 4 days later. No differences were found between the 3 hRV genotypes (hRV-A, hRV-B, and hRV-C) in symptom risk. A history of inhaled corticosteroid use, but not atopic status, mite allergen exposure, or vitamin D levels, modified the association between viruses and asthma symptoms. The detection of nasal hRV was associated with a significantly increased risk of day-to-day asthma symptoms in children. Host, virus genotype, and environmental factors each had only a small or no effect on the relationship of viral infections to asthma symptoms. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Dec 2014 · Journal of Allergy and Clinical Immunology
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    ABSTRACT: Over the last decade a convergent body of evidence has emerged from epidemiology, animal experiments and clinical trials which links low vitamin D status with a range of adverse neuropsychiatric outcomes. This research demonstrates that the timing of exposure to low vitamin D influences the nature of brain phenotypes, as exposures during gestation versus adulthood result in different phenotypes. With respect to early life exposures, there is robust evidence from rodent experiments indicating that transient developmental vitamin D (DVD) deficiency is associated with changes in brain structure, neurochemistry, gene and protein expression and behavior. In particular, DVD deficiency is associated with alterations in the dopaminergic neurotransmitter systems. In contrast, recently published animal experiments indicate that adult vitamin D (AVD) deficiency is associated with more subtle neurochemical and behavioral phenotypes. This paper explores key issues that need to be addressed in future research. There is a need to define the timing and duration of the ‘critical window’ during which low vitamin D status is associated with differential and adverse brain outcomes. We discuss the role for ‘two-hit hypotheses’, which propose that adult vitamin D deficiency leaves the brain more vulnerable to secondary adverse exposures, and thus may exacerbate disease progression. Finally, we explore the evidence implicating a role for vitamin D in rapid, non-genomic mechanisms that may involve L-type calcium channels and brain function.
    Full-text · Article · Nov 2014 · The Journal of Steroid Biochemistry and Molecular Biology
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    ABSTRACT: Background MicroRNAs (miRNAs) play a pivotal role in coordinating messenger RNA (mRNA) transcription and stability in almost all known biological processes, including the development of the central nervous system. Despite our broad understanding of their involvement, we still have a very sparse understanding of specifically how miRNA contribute to the strict regional and temporal regulation of brain development. Accordingly, in the current study we have examined the contribution of miRNA in the developing rat telencephalon and mesencephalon from just after neural tube closure till birth using a genome-wide microarray strategy. Results We identified temporally distinct expression patterns in both the telencephalon and mesencephalon for both miRNAs and their target genes. We demonstrate direct miRNA targeting of several genes involved with the migration, differentiation and maturation of neurons. Conclusions Our findings suggest that miRNA have significant implications for the development of neural structure and support important mechanisms that if disrupted, may contribute to or drive neurodevelopmental disorders. Electronic supplementary material The online version of this article (doi:10.1186/1471-2164-15-777) contains supplementary material, which is available to authorized users.
    Full-text · Article · Sep 2014 · BMC Genomics
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    ABSTRACT: Objective Low vitamin D status at birth may be associated with risk of adult onset multiple sclerosis, but this link has not been studied directly. We assessed the relation between neonatal vitamin D concentrations, measured in stored blood samples, and risk of multiple sclerosis.Methods This was a population-based case-control study in Sweden including 459 incident cases of multiple sclerosis and 663 controls, randomly drawn from a national population registry and frequency matched on sex, age, and residential area.ResultsThere was no association between neonatal 25-hydroxyvitamin D quintile and risk of multiple sclerosis (crude odds ratio = 1.0, 95% confidence interval = 0.68-1.44, for the highest quintile compared to the lowest). Adjusting for a number of potential confounding factors in early life (month of birth, latitude of birth, breastfeeding) and in adult life (25-hydroxyvitamin D, sun exposure, vitamin D intake from dairy products, fatty fish consumption, smoking, body mass index at 20 years of age) as well as ancestry, multiple sclerosis heredity, and socioeconomic group did not considerably affect the result.InterpretationAt a broad population level, 25-hydroxyvitamin D at birth was not associated with risk of multiple sclerosis. Ann Neurol 2014;76:338-346
    No preview · Article · Sep 2014 · Annals of Neurology
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    ABSTRACT: Repeated exposure to psychostimulants that either increase dopamine (DA) release or target N-methyl-D-aspartate (NMDA) receptors can induce behavioural sensitisation, a phenomenon that may be important for the processes of addiction and even psychosis. A critical component of behavioural sensitisation is an increase in DA release within mesocorticolimbic circuits. In particular, sensitisation to amphetamine leads to increased DA release within well-known sub-cortical brain regions and also regulatory regions such as prefrontal cortex (PFC). However, it is unknown how DA release within the PFC of animals is altered by sensitisation to NMDA receptor antagonists.
    Full-text · Article · Jul 2014 · Psychopharmacology
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    ABSTRACT: Context: Recognition that vitamin D might be associated with many chronic diseases has led to large-scale epidemiological and clinical studies. Dried blood spots (DBS) are a useful resource for these studies. Consequently, accurate, efficient and inexpensive assays to quantify 25-hydroxyvitamin D (25OHD) in DBS are required. Objective: This study evaluated the validity and reliability of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for measuring 25OHD in archived DBS, and compared measurements of 25OHD in DBS with those in plasma. Design and Participants: Sixty two participants in the Melbourne Collaborative Cohort Study who had plasma and matching DBS stored since study entry in the early 1990s were randomly selected for a study calibrating 25OHD concentrations in DBS with plasma. As part of a study of vitamin D and mortality, cancer and diabetes, we also assessed the reliability of measurements from DBS using 500 replicates placed randomly within 31 batches run over 15 months. Outcome measure: 25OHD concentrations measured by LC-MS/MS. Results: There was good agreement between measurements of 25OHD from DBS and plasma; R(2) = 0.73 from a regression of plasma concentration on DBS concentration. The within-batch and between-batch intra-class correlations from the 500 replicate measurements were 0.82 (95% CI: 0.80, 0.85) and 0.73 (95% CI: 0.68, 0.78), respectively. Conclusions: Measuring 25OHD in DBS is a valid and reliable alternative to measuring 25OHD in sera or plasma. A simple calibration model was developed to convert measurements from DBS to equivalent plasma measurements, thus enabling comparisons against clinical reference ranges and with studies using sera or plasma samples.
    Preview · Article · Jun 2014 · Journal of Clinical Endocrinology & Metabolism
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    ABSTRACT: Developmental vitamin D (DVD) deficiency has been proposed as a risk factor for schizophrenia. DVD-deficient rats show selective cognitive deficits and novelty-induced hyperlocomotion and enhanced locomotor responses from acute treatment with psychomimetic drugs, such as amphetamine and MK-801. Here we aimed to examine the effect of a drug from a different class of psychomimetic/psychoactive compounds, Δ-tetrahydrocannabinol (THC), on tasks of relevance to the cognitive and positive symptoms of schizophrenia. The aim of this study was to investigate whether DVD deficiency modulates the behavioural effects of THC on tests of delay-dependent memory, sensorimotor gating and locomotion. Adult control and DVD-deficient rats were injected with THC (0, 0.3, 0.6, 1.25, 2.5 mg/kg) 15 min before a delay match to sample (DMTS) task using variable delays (0-24 s). A separate group of rats was injected with either 2.5 mg/kg THC or vehicle before tests of either prepulse inhibition (PPI) of the acoustic startle response or in the open field. Control and DVD-deficient rats showed a similar dose-dependent impairment in performance on the DMTS. The greatest impairment was observed at 2.5 mg/kg for all delays (0-24 s). DVD-deficient rats showed THC-induced enhancement of PPI, which was not observed in control rats. There was no effect of maternal diet on acoustic startle response or locomotor responses in the open field. This study reports the novel findings that DVD-deficient rats were more sensitive to the acute effects of THC on PPI. It appears that prenatal vitamin D deficiency has long-term effects on sensitivity to the behavioural effects of cannabinoids.
    No preview · Article · Jun 2014 · Behavioural pharmacology
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    D.W. Eyles · P.Y. Liu · P. Josh · X. Cui
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    ABSTRACT: Apart from its role in regulating calcium there is growing evidence that vitamin D is a neuroactive steroid capable of regulating multiple pathways important for both brain development and mature brain function. Vitamin D induces its genomic effects through its nuclear receptor the vitamin D receptor (VDR). Although there is abundant evidence for this receptor’s presence in the mammalian brain from studies employing immunohistochemistry, Western blot or quantitative RNA studies there remains some dispute regarding the validity of these studies. In this study we provide unambiguous confirmation for the VDR in adult rodent brain using proteomic techniques. However Western blot experiments show that compared to more classic target organs such as the gut and kidney, VDR expression is quantitatively lower in the brain. In addition we have examined VDR subcellular distribution in the gut, kidney and brain from both embryonic and adult tissues. We show that in all embryonic tissues VDR distribution is mostly nuclear, however by adulthood it appears that at least in the gut and kidney, VDR presence in the plasma membrane is more prominent perhaps reflecting some change in VDR function with the maturation of these tissues. Finally the subcellular distribution of VDR in the embryo did not appear to be altered by vitamin D deficiency indicating that perhaps there are other mechanisms at play in vivo to stabilize this receptor in the absence of its ligand.
    Full-text · Article · May 2014 · Neuroscience
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    Darryl W. Eyles · Pei-Yun Liu · Peter Josh · Xiaoying Cui

    Full-text · Article · Mar 2014 · Neuroscience

  • No preview · Conference Paper · Jan 2014

Publication Stats

5k Citations
553.30 Total Impact Points

Institutions

  • 1994-2015
    • University of Queensland
      • • Queensland Brain Institute
      • • School of Biomedical Sciences
      • • Department of Medicine
      Brisbane, Queensland, Australia
  • 2012
    • University of Newcastle
      • School of Biomedical Sciences and Pharmacy
      Newcastle, New South Wales, Australia
  • 2003-2011
    • Griffith University
      Brisbane, Queensland, Australia
    • Mental Health Council of Australia
      Canberra, Australian Capital Territory, Australia
    • Schizophrenia Research Institute
      Darlinghurst, New South Wales, Australia
  • 1996
    • St. Marianna University School of Medicine
      Kawasaki Si, Kanagawa, Japan
  • 1992-1996
    • Princess Alexandra Hospital (Queensland Health)
      • Division of Medicine
      Brisbane, Queensland, Australia
    • Royal Brisbane Hospital
      Brisbane, Queensland, Australia