Abstract Developmental vitamin D (DVD)-deficiency is an epidemiologically established risk factor for autism. Emerging studies also highlight the involvement of gut microbiome/gut physiology in autism. The current study aims to examine the effect of DVD-deficiency on a broad range of autism-relevant behavioural phenotypes and gut health. Vitamin D deficient rat dams exhibited altered maternal care, DVD-deficient pups showed increased ultrasonic vocalizations and as adolescents, social behaviour impairments and increased repetitive self-grooming behaviour. There were significant impacts of DVD-deficiency on gut health demonstrated by alterations to the microbiome, decreased villi length and increased propionate levels. Overall, our animal model of this epidemiologically validated risk exposure for autism shows an expanded range of autism-related behavioural phenotypes and now alterations in gut microbiome that correlate with social behavioural deficits raising the possibility that DVD-deficiency induced ASD-like behaviours are due to alterations in gut health.
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.This study evaluated the validity and reliability of a liquid chromatography-tandem mass spectrometry assay for measuring 25OHD in archived DBS and compared measurements of 25OHD in DBS with those in plasma.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.25OHD concentrations were measured by liquid chromatography-tandem mass spectrometry.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 intraclass correlations from the 500 replicate measurements were 0.82 (95% confidence interval, 0.80, 0.85) and 0.73 (95% confidence interval, 0.68, 0.78), respectively.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.
Introduction: In every day life, sensory systems are exposed to an incredible amount of information. To protect the brain from being overwhelmed, this information is filtered so only relevant information gets processed and transformed into action. Sensorimotor gating is one such filter mechanism. It refers to the state-dependent regulation of transmission, or gating, of sensory information to motor systems. Impairments in sensorimotor gating, such as pre-pulse inhibition (PPI), have been described in several psychiatric disorders like schizophrenia, autism and ADHD. Methods: We study sensorimotor gating in Drosophila with a high-throughput behavioral paradigm that allows us to measure motor responses to moving visual stimuli in walking fruit flies. Groups of 25-30 flies are loaded into a maze placed over a screen showing moving visual stimuli. Flies move through the maze and pass eight successive left/right choice points after which they emerge in one of nine end tubeswhere they are counted. The average response is the Optomotor Index (OI). We measured the effect of briefly flashed visual stimuli on OI in two wildtype Drosophila strains: Canton-S and Berlin. Results: Flash duration varied from 13-106 ms (n=240 per condition). In both strains, only 40 ms black flashes against a green background significantly reduced OI. Additionally, fly behavior was recorded using custom-made fly-tracking software. During 40 ms black flashes, behavior changed considerably. Flies spend longer in the maze and backtracked more. Conclusions: We are currently investigating whether this behavioral change can be suppressed with a low intensity visual pre-pulse, in order to create a model of PPI in the fly. The development of such a model could be of enormous use given PPI deficits are considered a viable endophenotype of schizophrenia.
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