ORCID Profile
0000-0002-3436-0923
Current Organisation
University of Western Australia
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Publisher: International Society for Managing and Technical Editors (ISMTE)
Date: 06-2017
Publisher: Elsevier BV
Date: 2003
DOI: 10.1016/S0306-4522(03)00571-2
Abstract: The basic helix-loop-helix (bHLH) transcription factor stem cell leukaemia (SCL) is a 'master regulator' of haematopoiesis, where SCL is pivotal in cell fate determination and differentiation. SCL has also been detected in CNS, where other members of the bHLH-family have been shown to be indispensable for neuronal development however, no detailed expression pattern of SCL has so far been described. We have generated a map of SCL expression in the embryonic and adult mouse brain based on histochemical analysis of LacZ reporter gene expression in sequential sections of brain tissue derived from SCL-LacZ knockin mice. The expression of LacZ was confirmed to reflect SCL expression by in situ hybridisation. LacZ expression was found in a range of different diencephalic, mesencephalic and metencephalic brain nuclei in adult CNS. Co-localisation of LacZ with the neuronal marker NeuN indicated expression in post-mitotic neurons in adulthood. LacZ expression by neurons was confirmed in tissue culture analysis. The nature of the pretectal, midbrain and hindbrain regions expressing LacZ suggest that SCL in adult CNS is potentially involved in processing of visual, auditory and pain related information. During embryogenesis, LacZ expression was similarly confined to thalamus, midbrain and hindbrain. LacZ staining was also evident in parts of the intermediate and marginal zone of the aqueduct and ventricular zone of the fourth ventricle at E12.5 and E14. These cells may represent progenitor stages of differentiating neural cells. Given the presence of SCL in both the developing brain and in post-mitotic neurons, it seems likely that the function of SCL in neuronal differentiation may differ from its function in maintaining the differentiated state of the mature neuron.
Publisher: Elsevier BV
Date: 1988
DOI: 10.1016/0022-4731(88)90134-3
Abstract: In vitro cytosol binding, receptor autoradiography with radiolabelled corticosteroid analogs, and immunocytochemistry with monoclonal antibodies have revealed the presence of two receptor systems for corticosteroids in rat and hamster brains. The type I receptor is found mainly in the hippoc al region, and in the hamster it binds cortisol (F) and corticosterone (B) with similar affinity while in the rat (a species which unlike the hamster secretes solely B) the type I receptor shows high affinity to B and not to F. The type II receptor is more widely distributed in the brain and it binds to F (hamster) or B (rat) with affinity 4-6-fold lower than to the type I. in vivo, the hamster type I and II retain F much more than B while those in the rat show the opposite. In conclusion, the present study clearly indicates species-specificity in type I and type II receptor systems in these animals. Furthermore, the type I receptor displays in vivo stringent preference for retention of the animal's predominantly circulating corticosteroid (F in hamster, in B in rat).
Publisher: Cambridge University Press (CUP)
Date: 18-04-2011
DOI: 10.1017/S0954579411000241
Abstract: The maternal experience of stressful events during pregnancy has been associated with a number of adverse consequences for behavioral development in offspring, but the measurement and interpretation of prenatal stress varies among reported studies. The Raine Study recruited 2900 pregnancies and recorded life stress events experienced by 18 and 34 weeks' gestation along with numerous sociodemographic data. The mother's exposure to life stress events was further documented when the children were followed-up in conjunction with behavioral assessments at ages 2, 5, 8, 10, and 14 years using the Child Behavior Checklist. The maternal experience of multiple stressful events during pregnancy was associated with subsequent behavioral problems for offspring. Independent (e.g., death of a relative, job loss) and dependent stress events (e.g., financial problems, marital problems) were both significantly associated with a greater incidence of mental health morbidity between age 2 and 14 years. Exposure to stressful events in the first 18 weeks of pregnancy showed similar associations with subsequent total and externalizing morbidity to events reported at 34 weeks of gestation. These results were independent of postnatal stress exposure. Improved support for women with chronic stress exposure during pregnancy may improve the mental health of their offspring in later life.
Publisher: Hindawi Limited
Date: 26-07-2012
DOI: 10.4081/MI.2012.E21
Abstract: Genetic risk for depressive disorders is poorly understood despite consistent suggestions of a high heritable component. Most genetic studies have focused on risk associated with single variants, a strategy which has so far only yielded small (often non-replicable) risks for depressive disorders. In this paper we argue that more substantial risks are likely to emerge from genetic variants acting in synergy within and across larger neurobiological systems (polygenic risk factors). We show how knowledge of major integrated neurobiological systems provides a robust basis for defining and testing theoretically defensible polygenic risk factors. We do this by describing the architecture of the overall stress response . Maladaptation via impaired stress responsiveness is central to the aetiology of depression and anxiety and provides a framework for a systems biology approach to candidate gene selection. We propose principles for identifying genes and gene networks within the neurosystems involved in the stress response and for defining polygenic risk factors based on the neurobiology of stress-related behaviour. We conclude that knowledge of the neurobiology of the stress response system is likely to play a central role in future efforts to improve genetic prediction of depression and related disorders.
Publisher: Elsevier BV
Date: 1992
DOI: 10.1016/0197-4580(92)90024-R
Abstract: The present study examined the stress responsiveness of the hypothalamic-pituitary-adrenal axis in relation to the properties of corticosteroid receptors in the brain and pituitary of old (30 months) and young (3 months) male Brown Norway rats. Adrenocorticotropin hormone (ACTH) and corticosterone (B) were measured following exposure to novelty and to a conditioned emotional stimulus in blood s les sequentially obtained from chronically cannulated animals. Mineralocorticoid (MR) and glucocorticoid (GR) receptors were quantified by radioligand binding assay and in situ hybridization. The receptor binding constants were determined in tissue of rats that were adrenalectomized 24 hours previously, whereas gene expression was measured in the brain of intact animals. Aged Brown Norway rats showed a small but significant elevation in basal circulating ACTH level. The conditioned emotional stimulus, rather than the exposure to novelty, triggered a more than two-times higher ACTH response in the aged compared to the young rat. The termination of the stress-induced ACTH response seemed to proceed more efficiently in the aged rat. Basal and stress-induced total plasma B level did not differ in the young and old rats. The latter showed a 65% lower binding capacity of corticosteroid-binding globulin (CBG). Interestingly, in the aged rat the stress-induced rise in free circulating plasma B level was not elevated, but only prolonged. The hippoc us of aged rats displayed a decrease of maximally 44% in the apparent Bmax of MR, but no change in GR number. The Bmax of GR showed a 40% reduction in the hypothalamus and a 50% reduction in the anterior pituitary. GR affinity was considerably increased in the anterior pituitary, but was unchanged in the hippoc us and hypothalamus. Old age affected MR and GR gene expression differentially. GR mRNA was significantly reduced in cell field CA3 (-42%), CA4 (-41%) and the dentate gyrus (-26%) of the dorsal hippoc us, but did not change either in hippoc al cell field CA1 or in the hypothalamic paraventricular nucleus (PVN) of the old rat. There was no significant difference in MR mRNA between young and aged rats in the different cell fields of the hippoc us. The aged rat, therefore, is characterized by site- and receptor-specific changes in binding constants as well as by changes in receptor transcription and translation. The data demonstrate that in the old Brown Norway rats, a conditioned emotional stimulus results in enhanced pituitary ACTH release.(ABSTRACT TRUNCATED AT 400 WORDS)
Publisher: Elsevier BV
Date: 08-2000
DOI: 10.1016/S0009-9120(00)00155-7
Abstract: We developed a quantitative reverse-transcription polymerase chain reaction (RT-PCR) to determine CK20 expression in colorectal tumor and hematopoietic tissue. Our method incorporates a calibrated PCR with an internal competitor and an external standard. The RT-PCR assay is sensitive detecting 10 target molecules of CK20 in solution with one round of 38 lification cycles. Genomic DNA contamination was eliminated by Dnase I digestion of total RNA. The inclusion of a calibrator in the quantitative RT-PCR analysis allowed for a high throughput of unknown s les within the same assay improving comparative analysis between the s les tested. Analysis of peripheral blood and bone marrow from 20 healthy volunteers revealed a low level of CK20 expression in all s les. To study the clinical significance of CK20 expression as a marker of systemic metastatic disease it is essential to measure CK20 mRNA levels in hematopoietic tissue with sensitive quantitative RT-PCR. A sensitive and reproducible method, which is easily performed, is described.
Publisher: Informa UK Limited
Date: 03-2011
Publisher: Elsevier BV
Date: 07-1991
DOI: 10.1016/0165-3806(91)90111-U
Abstract: In situ hybridization was used to study the neuroanatomical distribution of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) gene expression during development in the rat. This study was based on incubation of adjacent sections of brains from 2-, 8-, 12-, 16-day-old and adult (3 months) rats with 35S-labelled cRNA probes. These probes are transcribed from 513 and 500 basepair cDNA fragments with little homology from rat brain MR and rat liver GR respectively. Different patterns of expression were found in the brain of MR and GR during ontogeny. At postnatal day (pnd) 2, a high density of labelled MR mRNA was found in all pyramidal (CA1-4) and granular (dentate gyrus) cell fields of the hippoc al structure, the anterior hippoc us and indusium griseum, and cortex layer II. Modest to high labelling of MR mRNA was observed in the subfornical organ and the anterior hypothalamus. A variety of other telencephalic regions anterior and posterior of bregma exhibited modest to weak intensity of labelled MR mRNA. The diencephalon virtually lacked labelled MR mRNA. At older postnatal ages including the adult age, this regional distribution of radiolabelled MR mRNA did not change. At pnd 2, abundant radiolabelled GR mRNA was found widespread over the tel- and diencephalon, with the highest density observed in cell field CA1 and CA2 of the hippoc us and the parvocellular ision of the hypothalamic paraventricular nucleus. Modestly labelled GR mRNA was observed in various hypothalamic and thalamic nuclei, basal ganglia, the lateral septum and the amygdala. At older postnatal ages and in adulthood, the intensity of labelled GR mRNA became progressively stronger in the hippoc us. Moreover, we observed a trend towards a more condensed and narrow band of cell bodies in the hippoc us for both MR and GR mRNA during ontogeny. A semi-quantitative comparison of the intensity of both labelled mRNA's performed at each age revealed a significantly lower expression of GR than MR mRNA in the CA3 cell field at pnd 2. At pnd 8 and 12, the amount of GR mRNA was significantly lower in the dentate gyrus and the CA3, whereas in adulthood, less GR mRNA was measured in all pyramidal and granular cell fields. The present study demonstrates that MR and GR genes are expressed in early postnatal development in a pattern resembling that in adulthood. As is the case in the adult brain, there is more MR than GR mRNA in the hippoc us during ontogeny, especially in the CA3 cell field and the DG.
Publisher: Wiley
Date: 04-2006
DOI: 10.1111/J.1460-9568.2006.04712.X
Abstract: Abstract The basic helix-loop-helix (bHLH) transcription factor Scl displays tissue-restricted expression and is critical for the establishment of the haematopoietic system loss of Scl results in embryonic death due to absolute anaemia. Scl is also expressed in neurons of the mouse diencephalon, mesencephalon and metencephalon however, its requirement in those sites remains to be determined. Here we report conditional deletion of Scl in neuronal precursor cells using the Cre/LoxP system. Neuronal-Scl deleted mice died prematurely, were growth retarded and exhibited an altered motor phenotype characterized by hyperactivity and circling. Moreover, ablation of Scl in the nervous system affected brain morphology with abnormal neuronal development in brain regions known to express Scl under normal circumstances there was an almost complete absence of Scl-null neurons in the hindbrain and partial loss of Scl-null neurons in the thalamus and midbrain from early neurogenesis onwards. Our results demonstrate a crucial role for Scl in the development of Scl-expressing neurons, including gamma-aminobutyric acid (GABA)ergic interneurons. Our study represents one of the first demonstrations of functional overlap of a single bHLH protein that regulates neural and haematopoietic cell development. This finding underlines Scl's critical function in cell fate determination of mesodermal as well as neuroectodermal tissues.
Publisher: Springer Science and Business Media LLC
Date: 08-1993
DOI: 10.1007/BF00711575
Publisher: Elsevier BV
Date: 12-1987
DOI: 10.1016/0006-8993(87)91563-0
Abstract: The localization of the glucocorticoid receptor (GR) (type 2) in the rat brain was studied with immunocytochemistry using a monoclonal antibody against the rat liver GR. Strong GR immunoreactivity (GR-ir) was observed in neurons of limbic and brainstem structures known to be associated with the stress-activated circuitry, which suggest that these sites are responsive to glucocorticoid feedback. The intracellular localization of GR-ir was examined in CA1 and CA2 pyramidal neurons of the hippoc us. In intact rats GR-ir is predominantly present in the cell nucleus. Adrenalectomy (ADX) caused a slow depletion of the GR-ir signal from the cell nucleus until near detection limits at two weeks postsurgery. At that time, 1 h after administration to longterm ADX rats the synthetic glucocorticoid (type 2) agonist RU 28362 as well as a moderate and high dose of corticosterone (CORT) markedly enhanced the cell nuclear GR-ir. The type 2 antagonist RU 38486 also caused an increase of GR immunostaining in cell nuclei upon acute administration to ADX rats. The mineralocorticoid aldosterone (ALDO) and a low dose of CORT, which bind almost exclusively to type 1 corticosteroid receptors, were ineffective. In conclusion, our data suggest that in the hippoc al CA1-2 neurons type 1 and type 2 corticosteroid receptors may coexist. The steroid-induced changes in cell nuclear immunoreactive GR staining intensity suggest possible cytoplasmic-cell nuclear translocation of GR and/or exposure of immunogenic GR domains.
Publisher: Springer Science and Business Media LLC
Date: 13-11-2012
Publisher: Springer Science and Business Media LLC
Date: 10-03-2009
DOI: 10.1007/S00213-009-1509-4
Abstract: Behavioural evidence supports the notion that oral glucose ingestion enhances recognition memory judgements based on recollection, but not familiarity. The present study sought to clarify and extend upon these behavioural findings by investigating the influence of glucose administration on event-related potential (ERP) components that are thought to be differentially mediated by recollection and familiarity processes in healthy adolescents. In a within-subjects design, participants performed a recognition memory task, during which time electroencephalogram (EEG) was recorded, subsequent to ingestion of either (a) glucose or (b) placebo in a counterbalanced order. Response times during the recognition memory task were observed to be faster for the glucose condition, relative to a placebo control. Further, glucose ingestion was associated with an enhanced left parietal old/new ERP effect (a marker of recollection) and an enhanced mid-frontal old/new ERP effect (known to be mediated by familiarity). These findings (a) support the results of previous research that the 'glucose memory facilitation effect' can be extended to healthy adolescents, but (b) suggest that glucose enhances both the recollection and familiarity components of recognition memory. The observed ERP profile has important implications for the proposal that glucose specifically targets the hippoc us in modulating cognitive performance.
Publisher: Elsevier BV
Date: 07-1988
DOI: 10.1016/0165-3806(88)90207-6
Abstract: The ontogeny of the Type 2 glucocorticoid receptor (GR) in the rat brain was examined using a monoclonal antibody raised against the rat liver GR. Marked changes both in the intensity and in the localization of GR immunoreactivity (GR-ir) were found to occur as a function of age and brain area examined. First, GR-ir was high perinatally and decreased to a low intensity of immunostaining around postnatal day 12 (pnd 12). Thereafter, GR-ir increased to a moderate intensity, which resembled adult levels by pnd 20 in most brain areas. Second, in some regions, such as the hippoc al CA3-4 pyramidal cell fields and the suprachiasmatic nucleus of the hypothalamus, GR-ir was only clearly present during the first postnatal week. Third, in the hippoc us, GR-ir localization showed a distinctive developmental trend towards greater compactness within the CA1-2 pyramidal cell fields and a greater restriction of immunoreactive staining to these cell fields with exclusion of the adjoining areas. Fourth, adrenalectomy reduced overall GR-immunopositive staining, which could be reversed by administration of the selective glucocorticoid agonist, RU 28362. Our results suggest that during ontogeny the glucocorticoid receptor system displays considerable plasticity. Such plasticity may provide a basis for understanding the role of glucocorticoids during brain development.
Publisher: SAGE Publications
Date: 25-11-2009
Abstract: Glucose administration is associated with memory enhancement in healthy young in iduals under conditions of ided attention at encoding. While the specific neurocognitive mechanisms underlying this ‘glucose memory facilitation effect’ are currently uncertain, it is thought that in idual differences in glucoregulatory efficiency may alter an in idual’s sensitivity to the glucose memory facilitation effect. In the present study, we sought to investigate whether basal hypothalamic–pituitary–adrenal axis function (itself a modulator of glucoregulatory efficiency), baseline self-reported stress and trait anxiety influence the glucose memory facilitation effect. Adolescent males (age range = 14–17 years) were administered glucose and placebo prior to completing a verbal episodic memory task on two separate testing days in a counter-balanced, within-subjects design. Glucose ingestion improved verbal episodic memory performance when memory recall was tested (i) within an hour of glucose ingestion and encoding, and (ii) one week subsequent to glucose ingestion and encoding. Basal hypothalamic–pituitary–adrenal axis function did not appear to influence the glucose memory facilitation effect however, glucose ingestion only improved memory in participants reporting relatively higher trait anxiety. These findings suggest that the glucose memory facilitation effect may be mediated by biological mechanisms associated with trait anxiety.
Publisher: Elsevier BV
Date: 03-2009
DOI: 10.1016/J.BBI.2008.12.004
Abstract: Although there are recognised associations between psychological and immune function, the effects of maternal depressive symptoms on fetal immune development have not been investigated. This study examined the relationship between maternal depression scores as assessed by the Beck Depression Inventory (BDI) in the second trimester and measure of neonatal immune function measured in cord blood. This study was conducted in a cohort of women (n=83) who had received either fish oil containing 3.7 g/day n-3 polyunsaturated fatty acid (n-3PUFA) or a placebo from 20 weeks gestation as part of a randomised controlled trial. At 20 weeks gestation, prior to the intervention, 22% of women in the study manifested mild to moderate depressive symptoms (BDI > or =10). Neonates of these women had higher lymphoproliferative responses to a range of stimuli (including egg ovalbumin and cat allergen) compared with neonates of women with normal BDI scores (<10). These neonates also showed higher spontaneous cytokine production including (IL-6 and IL-10) and higher stimulated cytokine responses to both bacterial antigens and allergens. These patterns were evident after allowing for maternal age and education, parity, gestation, infant gender, delivery method and neonatal n-3/n-6 PUFA status. This exploratory study supports the notion that maternal mood in pregnancy may have the potential to influence fetal immune development. Further studies are needed to determine the significance of this.
Publisher: Cambridge University Press (CUP)
Date: 06-2008
DOI: 10.1017/S0140525X08004135
Abstract: The authors of this commentary concur with the viewpoint presented by Mareschal et al. (2007a 2007b) concerning the relevance of neurological data when theorizing about cognitive development. However, we argue here that Mareschal et al. fail to consider adequately the relevance of reorganizational brain events occurring through adolescence and early adulthood, especially regarding the prefrontal cortex and the ontogeny of executive functioning. In addition, evidence from the lifespan neurodevelopmental literature indicates that increased activity of neural networks may signify less efficient processing. This observation is of potential relevance when considering the neurological changes associated with cognitive development during childhood and adolescence.
Publisher: S. Karger AG
Date: 1988
DOI: 10.1159/000124954
Abstract: In vivo and in vitro autoradiography with radiolabeled corticosteroid analogs as well as immunocytochemistry with monoclonal antibodies raised against the rat liver glucocorticoid receptor were used to determine the presence and the topography of two corticosteroid receptor systems (type I and type II) in hamster and rat brains. In the rat, the in vivo autoradiograms clearly revealed the retention by the type I receptor of tracer amount of [3H]corticosterone, primarily in the CA1 and CA2 cell field, dentate gyrus and lateral septum. In the hamster, tracer doses of [3H]cortisol were retained not only in the CA1, CA2, dentate gyrus and lateral septum, but also at high level in the CA3 and CA4 areas. In both species, immunocytochemistry showed the widespread distribution of the type II receptor sites in areas such as the hippoc us, lateral septum, hypothalamus (particularly in the paraventricular nucleus), thalamus and cortex (these results were also reflected in the in vitro autoradiography). Strong cell nuclear glucocorticoid immunoreactivity (type II-IR) was observed in the CA1 and CA2 (as well as CA3 and CA4 in the hamster) pyramidal neurons. In the hippoc us of intact animals, type II-IR was seen in the neuronal cell nuclei. Adrenalectomy caused a depletion of the type II-IR signal from the cell nucleus, which returned 1 h following subcutaneous administration of RU 28362 to adrenalectomized animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: Elsevier BV
Date: 1991
DOI: 10.1016/0960-0760(91)90290-L
Abstract: The present study examined the stress responsiveness of the hypothalamic-pituitary-adrenal axis in relation to the properties of corticosteroid receptors in the brain and pituitary in old (30 months) and young (3 months) male Brown Norway rats. The data demonstrate that circulating ACTH rather than the corticosteroid plasma level was elevated under basal conditions and following stress. Furthermore, a reduction of mineralocorticoid receptor (MR) number in the hippoc us and of glucocorticoid receptor (GR) number in the hypothalamus and the pituitary correspond to increased neuroendocrine responsiveness and negative feedback following stress. The changes in receptor binding do not parallel the changes in the amount of MR and GR mRNA measured with in situ hybridization. This suggests that the processing rather than the receptor gene expression is affected in senescence.
Publisher: Elsevier BV
Date: 03-2013
DOI: 10.1016/J.JPEDS.2012.09.007
Abstract: To test the hypothesis that maternal antenatal exposure to life stress events is associated with lower achievement in literacy and numeracy at age 10 years, with sex differences in this link. The Western Australian Pregnancy Cohort Study recruited 2900 women at 18 weeks' pregnancy, and 2868 children were followed up at birth and postnatally. At age 10 years, information on 1038 children was linked to their literacy and numeracy test scores. Multivariate regression models were used to test the foregoing hypotheses, adjusting for important confounders. In girls, maternal antenatal exposure to 4 or more maternal life stress events or death of the mother's friend and/or relative was associated with lower reading scores. In contrast, exposure to 3 or more life stress events or to a pregnancy or financial problem was associated with higher reading scores in boys. Furthermore, maternal exposure to 4 or more life stress events was associated with higher mathematic scores and a residential move was linked to higher writing scores in boys. Maternal antenatal exposure to life stress events has differing effects on the school performance of male and female offspring. Further research is needed to explore the reasons for this sex difference.
Publisher: Wiley
Date: 2007
DOI: 10.1002/DVG.20274
Abstract: The Cre/LoxP system provides a powerful tool to investigate gene function in vivo. This system requires Cre-recombinase expressing mouse lines that permit control of gene recombination in a tissue-specific and time-dependent manner. To allow spatio-temporal gene deletion in specific central nervous system (CNS) neuronal populations, we generated mice with a tamoxifen-inducible Cre (Cre-ER(T)) transgene under control of the Scl/Tal1 neural promoter/enhancer -0.9E3 (-0.9E3CreER(T) transgenic mice). Using Cre-reporter mice we have shown that tamoxifen-mediated Cre-ER(T) recombination in -0.9E3CreER(T) mice recapitulated the anticipated expression pattern of Scl in the caudal thalamus, midbrain, hindbrain, and spinal cord. Cre-mediated recombination was also effectively induced during embryogenesis and marked the same population of neurons as observed in the adult. Additionally, we identified a tamoxifen-independent constitutively active -0.9E3CreER(T) mouse line that will be useful for gene deletion during early neurogenesis. These -0.9E3CreER(T) mice will provide tools to investigate the role of neuronal genes in the developing and mature CNS. CNS.
Publisher: Elsevier BV
Date: 06-2001
No related grants have been discovered for Anke van Eekelen.