ORCID Profile
0000-0001-6929-6258
Current Organisations
Mater Research
,
University of Tasmania
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Cellular Nervous System | Central Nervous System | Neurosciences
Publisher: Frontiers Media SA
Date: 2015
Publisher: Public Library of Science (PLoS)
Date: 30-01-2013
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.BBR.2019.01.009
Abstract: Maternal alcohol consumption throughout pregnancy can result in long term behavioural deficits in offspring. However, less is known about the impact of alcohol during the periconceptional period (PC). The aim of this study was to examine the effect of PC ethanol (PC:EtOH) exposure on long term cognitive function including memory and anxiety. Rats were exposed to a liquid diet containing ethanol (EtOH) (12.5% vol vol) or a control diet from 4 days prior to mating until day 4 of pregnancy. Separate cohorts of animals were tested at 6 months (adult) or 15-18 months of age (aged). Offspring underwent a series of behavioural tests to assess anxiety, spatial and recognition memory. The hippoc us was collected, and mRNA expression of epigenetic modifiers and genes implicated in learning and memory were examined. PC:EtOH exposure resulted in a subtle anxiety like behaviour in adult female offspring with a significant reduction in directed exploring/head dipping behaviour during holeboard testing. In aged male offspring, PC:EtOH exposure resulted in a tendency for increased directed exploring/head dipping behaviour during holeboard testing. No differences between treatments were observed in the elevated plus maze. Aged female offspring exposed to PC:EtOH demonstrated short term spatial memory impairment (P < 0.05). PC:EtOH resulted in an upregulation of hippoc al mRNA expression of bdnf, grin2a and grin2b at 18 months of age along with increased expression of epigenetic modifiers (dnmt1, dnmt3a and hdac2). In conclusion, PC:EtOH can lead to sex specific anxiety-like behaviour and impairments in spatial memory and altered hippoc al gene expression.
Publisher: Wiley
Date: 16-04-2019
DOI: 10.1002/GLIA.23620
Publisher: Public Library of Science (PLoS)
Date: 30-06-2014
Publisher: Frontiers Media SA
Date: 16-11-2018
Publisher: Public Library of Science (PLoS)
Date: 09-06-2016
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.MCN.2016.09.002
Abstract: The amyloid-β precursor protein (APP) is a transmembrane protein that is widely expressed within the central nervous system (CNS). While the pathogenic dysfunction of this protein has been extensively studied in the context of Alzheimer's disease, its normal function is poorly understood, and reports have often appeared contradictory. In this study we have examined the role of APP in regulating neurogenesis in the adult mouse brain by comparing neural stem cell proliferation, as well as new neuron number and morphology between APP knockout mice and C57bl6 controls. Short-term EdU administration revealed that the number of proliferating EdU
Publisher: Wiley
Date: 24-12-2021
DOI: 10.1002/GLIA.23957
Publisher: Frontiers Media SA
Date: 13-11-2020
Publisher: Frontiers Media SA
Date: 05-04-2016
Publisher: Wiley
Date: 18-06-2020
DOI: 10.1002/JNR.24672
Publisher: Elsevier BV
Date: 12-2017
Publisher: Springer Science and Business Media LLC
Date: 03-08-2022
DOI: 10.1186/S13063-022-06526-Z
Abstract: Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease, characterised by oligodendrocyte death and demyelination. Oligodendrocyte progenitor cells can differentiate into new replacement oligodendrocytes however, remyelination is insufficient to protect neurons from degeneration in people with MS. We previously reported that 4 weeks of daily low-intensity repetitive transcranial magnetic stimulation (rTMS) in an intermittent theta-burst stimulation (iTBS) pattern increased the number of new myelinating oligodendrocytes in healthy adult mice. This study translates this rTMS protocol and aims to determine its safety and tolerability for people living with MS. We will also perform magnetic resonance imaging (MRI) and symptom assessments as preliminary indicators of myelin addition following rTMS. Participants ( N = 30, aged 18–65 years) will have a diagnosis of relapsing-remitting or secondary progressive MS. ≤2 weeks before the intervention, eligible, consenting participants will complete a physical exam, baseline brain MRI scan and participant-reported MS symptom assessments [questionnaires: Fatigue Severity Scale, Quality of Life (AQoL-8D), Hospital Anxiety and Depression Scale and smartphone-based measures of cognition (electronic symbol digit modalities test), manual dexterity (pinching test, draw a shape test) and gait (U-Turn test)]. Participants will be pseudo-randomly allocated to rTMS ( n =20) or sham (placebo n =10), stratified by sex. rTMS or sham will be delivered 5 days per week for 4 consecutive weeks (20 sessions, 6 min per day). rTMS will be applied using a 90-mm circular coil at low-intensity (25% maximum stimulator output) in an iTBS pattern. For sham, the coil will be oriented 90° to the scalp, preventing the magnetic field from stimulating the brain. Adverse events will be recorded daily. We will evaluate participant blinding after the first, 10th and final session. After the final session, participants will repeat symptom assessments and brain MRI, for comparison with baseline. Participant-reported assessments will be repeated at 4-month post-allocation follow-up. This study will determine whether this rTMS protocol is safe and tolerable for people with MS. MRI and participant-reported symptom assessments will serve as preliminary indications of rTMS efficacy for myelin addition to inform further studies. Australian New Zealand Clinical Trials Registry ACTRN12619001196134 . Registered on 27 August 2019
Publisher: Springer Science and Business Media LLC
Date: 30-05-2022
DOI: 10.1038/S42003-022-03470-1
Abstract: Oligodendrocyte progenitor cells (OPCs) express protocadherin 15 (Pcdh15), a member of the cadherin superfamily of transmembrane proteins. Little is known about the function of Pcdh15 in the central nervous system (CNS), however, Pcdh15 expression can predict glioma aggression and promote the separation of embryonic human OPCs immediately following a cell ision. Herein, we show that Pcdh15 knockdown significantly increases extracellular signal-related kinase (ERK) phosphorylation and activation to enhance OPC proliferation in vitro. Furthermore, Pcdh15 knockdown elevates Cdc42-Arp2/3 signalling and impairs actin kinetics, reducing the frequency of lamellipodial extrusion and slowing filopodial withdrawal. Pcdh15 knockdown also reduces the number of processes supported by each OPC and new process generation. Our data indicate that Pcdh15 is a critical regulator of OPC proliferation and process motility, behaviours that characterise the function of these cells in the healthy CNS, and provide mechanistic insight into the role that Pcdh15 might play in glioma progression.
Publisher: Cambridge University Press (CUP)
Date: 17-10-2017
DOI: 10.1017/S2040174417000824
Abstract: Alcohol consumption around the time of conception is highly prevalent in Western countries. Exposure to ethanol levels during gestation has been associated with altered development of the mesolimbic reward pathway in rats and increased propensity to addiction, however the effect of exposure only around the time of conception is unknown. The current study investigated the effects of periconceptional alcohol exposure (PC:EtOH) on alcohol and palatable food preferences and gene expression in the ventral tegmental area (VTA) and the nucleus accumbens of the adult offspring. Rats were exposed to a liquid diet containing ethanol (EtOH) (12.5% vol/vol) or a control diet from 4 days before mating until 4 days after mating. PC:EtOH had no effect on alcohol preference in either sex. At 15 months of age, however, male PC:EtOH offspring consumed more high-fat food when compared with male control offspring, but this preference was not observed in females. Expression of the dopamine receptor type 1 ( Drd1a ) was lower in the VTA of male PC:EtOH offspring compared with their control counterparts. There was no effect of PC:EtOH on mRNA expression of the µ-opioid receptor, tyrosine hydroxylase ( Th ), dopamine receptor type 2 ( Drd2 ) or dopamine active transporter ( Slc6a3 ). These data support the hypothesis that periconceptional alcohol exposure can alter expression of key components of the mesolimbic reward pathway and heighten the preference of offspring for palatable foods and may therefore increase their propensity towards diet-induced obesity. These results highlight the importance of alcohol avoidance when planning a pregnancy.
Publisher: Elsevier BV
Date: 2021
DOI: 10.1016/J.CELREP.2020.108641
Abstract: Central nervous system myelination increases action potential conduction velocity. However, it is unclear how myelination is coordinated to ensure the temporally precise arrival of action potentials and facilitate information processing within cortical and associative circuits. Here, we show that myelin sheaths, supported by mature oligodendrocytes, remain plastic in the adult mouse brain and undergo subtle structural modifications to influence action potential conduction velocity. Repetitive transcranial magnetic stimulation and spatial learning, two stimuli that modify neuronal activity, alter the length of the nodes of Ranvier and the size of the periaxonal space within active brain regions. This change in the axon-glial configuration is independent of oligodendrogenesis and robustly alters action potential conduction velocity. Because aptitude in the spatial learning task was found to correlate with action potential conduction velocity in the fimbria-fornix pathway, modifying the axon-glial configuration may be a mechanism that facilitates learning in the adult mouse brain.
Publisher: The Royal Society
Date: 07-05-2015
Abstract: Ornamentation of parents poses a high risk for offspring because it reduces cryptic nest defence. Over a century ago, Wallace proposed that sexual dichromatism enhances crypsis of open-nesting females although subsequent studies found that dichromatism per se is not necessarily adaptive. We tested whether reduced female ornamentation in a sexually dichromatic species reduces the risk of clutch depredation and leads to adaptive parental roles in the red-capped plover Charadrius ruficapillus, a species with biparental incubation. Males had significantly brighter and redder head coloration than females. During daytime, when visually foraging predators are active, colour-matched model males incurred a higher risk of clutch depredation than females, whereas at night there was no difference in depredation risk between sexes. In turn, red-capped plovers maintained a strongly diurnal/nocturnal ision of parental care during incubation, with males attending the nest largely at night when visual predators were inactive and females incubating during the day. We found support for Wallace's conclusion that reduced female ornamentation provides a selective advantage when reproductive success is threatened by visually foraging predators. We conclude that predators may alter their prey's parental care patterns and therefore may affect parental cooperation during care.
Publisher: Elsevier BV
Date: 06-2017
DOI: 10.1016/J.BBR.2017.04.009
Abstract: It is well established that maternal undernutrition and micronutrient deficiencies can lead to altered development and behaviour in offspring. However, few studies have explored the implications of maternal Mg deficiency and programmed behavioural and neurological outcomes in offspring. We used a model of Mg deficiency (prior to and during pregnancy and lactation) in CD1 mice to investigate if maternal Mg deficiency programmed changes in behaviour and NMDAR subunit expression in offspring. Hippoc al tissue was collected at postnatal day 2 (PN2), PN8, PN21 and 6 months, and protein expression of NMDAR subunits GluN1, GluN2A and GluN2B was determined. At 6 months of age, offspring were subject to behavioural tasks testing aspects of anxiety-like behaviour, memory, and neophobia. Maternal hypomagnesemia was associated with increased GluN1, GluN2A and GluN2B subunit expression in female offspring at 6 months, but decreased GluN1 and GluN2A expression in males. The GluN2B:GluN2A expression ratio was increased in both sexes. Male (but not female) offspring from Mg-deficient dams showed anxiety-like behaviour, with reduced head dips (Suok test), and reduced exploration of open arms (elevated plus maze). Both male and female offspring from Mg-deficient dams also showed impaired recognition memory (novel object test). These findings suggest that maternal Mg deficiency can result in behavioural deficits in adult life, and that these changes may be related to alterations in hippoc al NMDA receptor expression.
Publisher: Wiley
Date: 14-04-2021
DOI: 10.1111/EJN.14726
Abstract: Myelin and axon losses are associated with cognitive decline in healthy ageing but are worse in people diagnosed with tauopathy. To determine whether tauopathy is also associated with enhanced myelin plasticity, we evaluated the behaviour of OPCs in mice that expressed a human pathological variant of microtubule‐associated protein tau ( MAPT P301S ). By 6 months of age (P180), MAPT P301S mice overexpressed hyperphosphorylated tau and had developed reactive gliosis in the hippoc us but had not developed overt locomotor or memory impairment. By performing cre‐lox lineage tracing of adult OPCs, we determined that the number of newborn oligodendrocytes added to the hippoc us, entorhinal cortex and fimbria was equivalent in control and MAPT P301S mice prior to P150. However, between P150 and P180, significantly more new oligodendrocytes were added to these regions in the MAPT P301S mouse brain. This large increase in new oligodendrocyte number was not the result of increased OPC proliferation, nor did it alter oligodendrocyte density in the hippoc us, entorhinal cortex or fimbria, which was equivalent in P180 wild‐type and MAPT P301S mice. Furthermore, the proportion of hippoc al and fimbria axons with myelin was unaffected by tauopathy. However, the proportion of myelinated axons that were ensheathed by immature myelin internodes was significantly increased in the hippoc us and fimbria of P180 MAPT P301S mice, when compared with their wild‐type littermates. These data suggest that MAPT P301S transgenic mice experience significant oligodendrocyte turnover, with newborn oligodendrocytes compensating for myelin loss early in the development of tauopathy.
Publisher: Public Library of Science (PLoS)
Date: 14-09-2016
Publisher: Elsevier BV
Date: 10-2021
DOI: 10.1016/J.SEMCDB.2021.03.017
Abstract: During cortical development and throughout adulthood, oligodendrocytes add myelin internodes to glutamatergic projection neurons and GABAergic inhibitory neurons. In addition to directing node of Ranvier formation, to enable saltatory conduction and influence action potential transit time, oligodendrocytes support axon health by communicating with axons via the periaxonal space and providing metabolic support that is particularly critical for healthy ageing. In this review we outline the timing of oligodendrogenesis in the developing mouse and human cortex and describe the important role that oligodendrocytes play in sustaining and modulating neuronal function. We also provide insight into the known and speculative impact that myelination has on cortical axons and their associated circuits during the developmental critical periods and throughout life, particularly highlighting their life-long role in learning and remembering.
Start Date: 2016
End Date: 2018
Funder: Multiple Sclerosis Research Australia
View Funded ActivityStart Date: 2018
End Date: 2021
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2017
End Date: 2019
Funder: Multiple Sclerosis Research Australia
View Funded ActivityStart Date: 2022
End Date: 2024
Funder: Australian Research Council
View Funded ActivityStart Date: 2021
End Date: 2015
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2018
End Date: 2020
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 02-2022
End Date: 02-2025
Amount: $428,000.00
Funder: Australian Research Council
View Funded Activity