Biomedical subjects

Thomas H J Burne

Publications and source records attributed to Thomas H J Burne.

12 recordsLinked to original sources

PubMed2006

Hyperlocomotion associated with transient prenatal vitamin D deficiency is ameliorated by acute restraint.

Transient prenatal vitamin D deficiency produces hyperlocomotion in the adult rat. The aim of this study was to examine the effects of acute restraint on the behaviour of DVD and control rats in the open field. Rats were conceived and born to developmentally vitamin D (DVD) deficient or replete (control) dams and, at 8 weeks of age, were monitored for 30 min in an open field using automated video tracking software. Half of the rats were restrained within a towel for 5 min immediately before the open field test. The remainder received minimal handling prior to the open field test. Repeating previous findings, DVD deficient animals had enhanced locomotion during the first 10 min of the open field test compared to control rats. By contrast, there were no differences in locomotor activity after acute restraint stress. The time rats spent in the corners and side of the open field was affected by prenatal diet. DVD rats spent less time in the corners and more time in the side than control rats across the whole 30 min test. This difference was not seen in rats with acute restraint stress. The time spent in the centre was not altered by prenatal diet or acute restraint. Thus, transient prenatal vitamin D deficiency induces a transient spontaneous hyperlocomotion in adulthood that is modulated by acute restraint stress.

Analysis of Variance↗

PubMed2006

Olfactory ability in the healthy population: reassessing presbyosmia.

Age-associated loss of olfactory function, or presbyosmia, has been described in many studies of olfactory ability. Presbyosmia has been ascribed to idiopathic causes despite recognition that many neurodegenerative diseases also induce loss of olfactory function and increase in incidence in the aged population. Often this olfactory loss is unnoticed or unreported by affected individuals. More effective olfactory function in women compared with men is another common feature of many studies of olfactory function. Here we report on normative data from an Australian population study (n = 942) that has been divided into 2 subpopulations and reassessed as (included) a population of healthy, nonmedicated, nonsmokers with no history of nasal problems (n = 485) and (excluded) a population of participants who were either medicated, smokers or had a history of nasal problems (n = 457). The "included" data set shows a strong relationship between self-reporting of olfactory sensitivity and olfactory function score. The included data set shows a small but significant decline in olfactory ability after 65 years of age and better olfactory function in females compared with males. Data from the excluded population show a marked decline in olfactory ability after 65 years of age, no difference between males and females, and a weak relationship between self-reporting of olfactory function and actual olfactory function. The power of this approach is that it provides a normative data set against which many factors such as medication schedules and pathological conditions can be compared.

Adolescent↗

PubMed2006

Developmental vitamin D deficiency alters MK 801-induced hyperlocomotion in the adult rat: An animal model of schizophrenia.

BACKGROUND: Developmental vitamin D (DVD) deficiency has been proposed as a risk factor for schizophrenia. The behavioral phenotype of adult rats subjected to transient low prenatal vitamin D is characterized by spontaneous hyperlocomotion but normal prepulse inhibition of acoustic startle (PPI). The aim of this study was to examine the impact of selected psychotropic agents and one well-known antipsychotic agent on the behavioral phenotype of DVD deplete rats. METHODS: Control versus DVD deplete adult rats were assessed on holeboard, open field and PPI. In the open field, animals were given MK-801 and/or haloperidol. For PPI, the animals were given apomorphine or MK-801. RESULTS: DVD deplete rats had increased baseline locomotion on the holeboard task and increased locomotion in response to MK-801 compared to control rats. At low doses, haloperidol antagonized the MK-801 hyperactivity of DVD deplete rats preferentially and, at a high dose, resulted in a more pronounced reduction in spontaneous locomotion in DVD deplete rats. DVD depletion did not affect either baseline or drug-mediated PPI response. CONCLUSIONS: These results suggest that DVD deficiency is associated with a persistent alteration in neuronal systems associated with motor function but not those associated with sensory motor gating. In light of the putative association between low prenatal vitamin D and schizophrenia, the discrete behavioral differences associated with the DVD model may help elucidate the neurobiological correlates of schizophrenia.

Acoustic Stimulation↗

PubMed2006

Developmental vitamin D (DVD) deficiency in the rat alters adult behaviour independently of HPA function.

Developmental vitamin D deficiency (DVD) has been shown to alter the orderly pattern of brain development. Even though the period of vitamin D deficiency is restricted to gestation this is sufficient to induce behavioural abnormalities in the adult offspring consistent with those seen in many animal models of schizophrenia. Given that some of these behavioural alterations could also be an indirect result of either impaired maternal hypothalamic pituitary axis (HPA) function (which in turn could influence maternal care) or the result of a permanent alteration in HPA function in the adult offspring we have examined HPA status in both maternal animals and adult offspring. In this study we have established that HPA function is normal in the maternally vitamin D deficient rat. We replicate the behavioural phenotype of hyperlocomotion whilst establishing that HPA function is also unchanged in the adult male offspring. We conclude that the behavioural alterations induced by DVD deficiency are due to some adverse event in brain development rather than via an alteration in stress response.

Animals↗

PubMed2005

Swimming behaviour and post-swimming activity in Vitamin D receptor knockout mice.

Animal experiments have shown that Vitamin D plays a role in both brain development and adult brain function. The adult Vitamin D receptor null mutant mouse (VDR -/-) is reported to be less active and more anxious than wild-type litter mate controls and to have poor swimming ability. However, an "anxious" behavioural phenotype is inferred from differences in locomotor behaviour. This is a general problem in behavioural phenotyping where a neurological phenotype is inferred from changes in locomotion which will be affected by non-neurological factors, such as muscle fatigue. In this study of VDR -/-, we conducted a detailed examination of one form of motor behaviour, swimming, compared to wildtype littermate controls. Swimming was assessed using a forced swim test, a laneway swimming test and a watermaze test using a visible platform. Post-swimming activity was assessed by comparing grooming and rearing behaviour before, and 5 min after, the forced swimming test. We replicated previous findings in which VDR -/- mice demonstrate more sinking episodes than wildtype controls in the forced swim test but they were similar to controls in the time taken to swim a 1m laneway, and in the time taken to reach a visible platform in the watermaze. Thus, the VDR -/- mice were able to swim but were not able to float. Grooming and rearing behaviour of the VDR -/- mice was similar to wildtype controls before the forced swim but the VDR -/- were much less active after the swim compared with wildtype mice which displayed high levels of grooming and rearing. We conclude that VDR -/- mice have muscular and motor impairments that do not affect their ability to swim but significantly alters the ability to float as well as their post-swimming activity. Differences in muscle strength may confound tests of activity that are used to infer an "anxious" phenotype.

Animals↗

PubMed2005

Effect of Y1 receptor deficiency on motor activity, exploration, and anxiety.

Neuropeptide Y (NPY) in the CNS plays an important regulatory role in anxiety-related responses as exogenous administration of NPY exerts an anxiolytic-like effect in rodents. This effect is believed to be mediated by the Y(1) receptor system as pharmacological modulation of this Y(1) receptor system results in an increase in anxiety. Here we present a comprehensive phenotyping strategy for characterizing Y(1) receptor knockout animals at different times of the circadian rhythm using several motor activity-, exploration-, and anxiety-related behavioural tasks including open field, elevated plus maze, light-dark, and hole board test. We show that Y(1) deficiency has an important effect on motor activity and explorative-like behaviours and that it results in marked alterations in anxiety-related behaviours. Importantly, the behavioural phenotype of the Y(1) receptor knockout mice is circadian rhythm-dependent and also influenced by stimuli such as restraint stress. In addition, we found evidence for increases in working memory. Taken together, these findings suggest an important role of Y(1) receptors in the regulation of motor activity, exploration, and anxiety-related behaviours. This role is also influenced by several factors such as circadian rhythm and stress exposure confirming the importance of a comprehensive strategy and of using genetic animal models in behavioural neuroscience.

Analysis of Variance↗

PubMed2005

Behavioural characterization of vitamin D receptor knockout mice.

Vitamin D (calcitriol) is a nuclear transcription regulator acting via a nuclear hormone receptor (VDR). In addition to its role in the regulation of calcium and phosphate homeostasis and in bone formation, Vitamin D is also thought to be involved in brain function. The aim of this study was to behaviourally phenotype VDR knockout mice. We characterized the behaviour of VDR null mutant mice and wildtype littermate controls by subjecting them to a range of tests including a primary behavioural screen (using the SHIRPA protocol), rotarod, gait analysis, Y-maze, marble burying test, bedding test, holeboard test, elevated plus maze, open field test and prepulse inhibition of the acoustic startle response. There were no effects of genotype on most of the scores from the SHIRPA protocol except that VDR -/- mice had alopecia, were shorter and weighed less than VDR +/+ mice. VDR -/- mice had a shorter gait as well as impairments on the rotarod, in the bedding test and impaired habituation in both the open field and on the acoustic startle response. The VDR -/- mice had normal acoustic startle responses but had impaired PPI at long (256 ms) but not short (64 ms) prepulse to pulse intervals. The VDR -/- mice were less active in the open field and buried fewer marbles in the marble burying test. However, there were no differences in the time spent on the open arms of the elevated plus maze or in working memory as assessed by repeat arm entries on the Y-maze. Therefore, it appears that VDR -/- mice have muscular and motor impairments that significantly affects locomotor behaviour but seemingly no impairments in cognition as indicated by exploration, working memory or anxiety.

Acoustic Stimulation↗

PubMed2004

Transient prenatal Vitamin D deficiency is associated with hyperlocomotion in adult rats.

Rat experiments have shown that prenatal Vitamin D deficiency leads to altered neonatal brain morphology, cell density and neurotrophin expression. In the current study we examined the hypothesis that Vitamin D deficiency during early development alters adult behaviour even when there is an intervening period in which the animal receives normal Vitamin D in later development. Rats were conceived and born to Vitamin D deficient dams (Birth); conceived, born and weaned from Vitamin D deficient dams (Weaning); or deficient in Vitamin D from conception to 10 weeks of age (Life). Litters were standardized to three males and three females per litter. All rat offspring were rendered normocalcaemic with calcium supplemented water (2 mM) after weaning. Control animals were born to mothers fed a normal diet but subject to similar litter size and calcium supplementation. At 10 weeks all animals were tested on the holeboard test, elevated plus maze test, social interaction observation, acoustic startle response test, prepulse inhibition of the acoustic startle response and a forced swim test. Early Vitamin D deficiency (Birth group) enhanced locomotion in the holeboard test and increased activity in the elevated plus maze. Thus, transient prenatal Vitamin D deficiency induces hyperlocomotion in adulthood, without severe motor abnormalities.

Acoustic Stimulation↗

PubMed2004

Vitamin D3-implications for brain development.

There is growing evidence that 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) is active in the brain but until recently there was a lack of evidence about its role during brain development. Guided by certain features of the epidemiology of schizophrenia, our group has explored the role of 1,25(OH)(2)D(3) in brain development using whole animal models and in vitro culture studies. The expression of the vitamin D receptor (VDR) in the embryonic rat brain rises steadily between embryonic day 15-23, and 1,25(OH)(2)D(3) induces the expression of nerve growth factor and stimulates neurite outgrowth in embryonic hippocampal explant cultures. In the neonatal rat, low prenatal vitamin D(3) in utero leads to increased brain size, altered brain shape, enlarged ventricles, reduced expression of nerve growth factors, reduced expression of the low affinity p75 receptor and increased cellular proliferation. In summary, there is growing evidence that low prenatal levels of 1,25(OH)(2)D(3) can influence critical components of orderly brain development. It remains to be seen if these processes are of clinical relevance in humans, but in light of the high rates of hypovitaminosis D in pregnant women and neonates, this area warrants further scrutiny.

Animals↗

PubMed2004

Combined prenatal and chronic postnatal vitamin D deficiency in rats impairs prepulse inhibition of acoustic startle.

There is growing evidence that 1,25-dihydroxyvitamin D3 is involved in normal brain development. The aim of this study was to examine the impact of prenatal and postnatal hypovitaminosis D on prepulse inhibition (PPI) of acoustic startle in adult rats. We compared six groups of rats: control rats with normal vitamin D throughout life and normal litter size (Litter); control rats with normal vitamin D but with a reduced litter size of two (Control); offspring from reduced litters of vitamin D deplete mothers who were repleted at birth (Birth), repleted at weaning (Weaning) or remained on a deplete diet until 10 weeks of age (Life); or control rats that were placed on a vitamin D-deficient diet from 5 to 10 weeks of age (Adult). All rats were tested in acoustic startle chambers at 5 and 10 weeks of age for acoustic startle responses and for PPI. There were no significant group differences at 5 weeks of age on the acoustic startle response or on PPI. At 10 weeks of age, rats in the Life group only had impaired PPI despite having normal acoustic startle responses. We conclude that combined prenatal and chronic postnatal hypovitaminosis D, but not early life hypovitaminosis D, alters PPI.

Acoustic Stimulation↗

PubMed2003

The neurodevelopmental hypothesis of schizophrenia: a review of recent developments.

The neurodevelopmental hypothesis (NDH) of schizophrenia suggests that a disruption of brain development during early life underlies the later emergence of psychosis during adulthood. The aim of this review is to chart the challenges and subsequent refinements to this hypothesis, with particular reference to the static versus progressive nature of the putative neurobiological processes underlying the NDH. A non-systematic literature review was undertaken, with an emphasis on major review papers relevant to the NDH. Weaknesses in the explanatory power of the NDH have led to a new generation of more refined hypotheses in recent years. In particular, recent versions of the hypothesis have incorporated evidence from structural neuroimaging which suggests changes in brain volumes after the onset of schizophrenia. More detailed models that incorporate progressive neurobiological processes have replaced early versions of the NDH, which were based on a 'static encephalopathy'. In addition, recent models have suggested that two or more 'hits' are required over the lifespan rather than only one early-life event. Animal models are providing important insights into the sequelae of disturbed early brain development. The NDH has provided great impetus to the schizophrenia research community. Recent versions of the hypothesis have encouraged more focused and testable hypotheses.

Animals↗

PubMed2002

Chemosensory input and lateralization of brain function in the domestic chick.

One-day old domestic chicks (Gallus gallus domesticus) show concentration-dependent behavioural responses to olfactory cues. In the present study we investigated the lateralized olfactory responses of 1-day-old chicks to the odours of eugenol and iso-amyl acetate. In experiment 1 different concentrations of each odour were presented in repeated trials to chicks housed individually. The odours were presented together with a small coloured bead at which the chick pecked. When tested with the highest concentration of eugenol (100% v/v), the chicks demonstrated more head shaking when their left nostril was occluded (RN; right nostril in use) than when their right nostril was occluded (LN; left nostril in use). No such lateralization occurred in response to iso-amyl acetate. This result was confirmed in a second experiment in which the chicks were tested with unscented stimuli, 100% eugenol and 100% isoamyl acetate. In experiment 3 we found that occluding both the chicks' nostrils abolished the head shaking response to eugenol and to iso-amyl acetate. Thus, the chicks' head shaking responses to the odorants eugenol and iso-amyl acetate are mediated primarily by inputs from within the nasal cavity, and not by oral or occular inputs. The present results are consistent with the hypothesis that there is lateralization to olfactory cues and that it is dependent on the involvement of receptors inside the nasal cavity. We suggest that differences in lateralized olfactory responses to different odours are affected by the relative involvement of intranasal olfactory and trigeminal chemoreceptors.

Animals↗