ORCID Profile
0000-0002-5615-3546
Current Organisations
UQ Queensland Brain Institute
,
Mater Medical Research Institute- UQ
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Central Nervous System | Medical Biochemistry and Metabolomics | Regenerative Medicine (incl. Stem Cells and Tissue Engineering) | Medical Biochemistry and Metabolomics not elsewhere classified | Nanobiotechnology
Cardiovascular System and Diseases | Nervous System and Disorders | Blood Disorders |
Publisher: American Society for Microbiology
Date: 26-02-2015
Abstract: We report here the first genome assembly and annotation of the human-pathogenic fungus Scedosporium aurantiacum, with a predicted 10,525 genes, and 11,661 transcripts. The strain WM 09.24 was isolated from the environment at Circular Quay, Sydney, New South Wales, Australia.
Publisher: Frontiers Media SA
Date: 2013
Publisher: Wiley
Date: 09-06-2012
DOI: 10.1002/DNEU.22027
Abstract: Resident populations of stem and precursor cells drive the production of new neurons in the adult hippoc us. Recent discoveries have highlighted that a large proportion of these precursor cells are in fact quiescent and can be activated by distinct neuronal activity under both normal physiological and pathological conditions. As growing evidence indicates that newborn neurons play a critical role in cognitive functions such as learning and memory and in mood regulation, it is paramount that we obtain a better understanding of how the reservoirs of stem and precursor cells are maintained and activated. In this review, we critically examine the roles of key molecular mechanisms that have been shown to regulate hippoc al precursor cells, especially their activation. We believe that understanding the mechanistic details of the activity-driven regulation of precursor cells will equip us with the ability to develop tailored strategies to trigger the generation of new neurons, thereby improving the functional outcomes in various neurological and psychiatric conditions.
Publisher: Elsevier BV
Date: 12-2000
DOI: 10.1016/S0925-4773(00)00487-1
Abstract: We have shown that the basic helix-loop-helix transcription factor Atonal is sufficient for specification of one of the three subsets of olfactory sense organs on the Drosophila antenna. Misexpression of Atonal in all sensory precursors in the antennal disc results in their conversion to coeloconic sensilla. The mechanism by which specific sense organ fate is triggered remains unclear. We have shown that the homeodomain transcription factor Cut which acts in the chordotonal-external sense organ choice does not play a role in olfactory sense organ development. The expression of atonal in specific domains of the antennal disc is regulated by an interplay of the patterning genes, Hedgehog and Wingless, and Drosophila epidermal growth factor receptor pathway.
Publisher: Informa UK Limited
Date: 08-04-2015
DOI: 10.1586/14787210.2015.1025055
Abstract: Community-acquired Acinetobacter baumannii (CA-Ab) is a rare but serious cause of community-acquired pneumonia in tropical regions of the world. CA-Ab infections predominantly affect in iduals with risk factors, which include excess alcohol consumption, diabetes mellitus, smoking and chronic lung disease. CA-Ab pneumonia presents as a surprisingly fulminant course and is characterized by a rapid onset of fever, severe respiratory symptoms and multi-organ dysfunction, with a mortality rate reported as high as 64%. It is unclear whether the distinct clinical syndrome caused by CA-Ab is because of host predisposing factors or unique bacterial characteristics, or a combination of both. Deepening our understanding of the drivers of overwhelming CA-Ab infection will provide important insights into preventative and therapeutic strategies.
Publisher: Society for Neuroscience
Date: 17-02-2010
DOI: 10.1523/JNEUROSCI.3780-09.2010
Abstract: Adult hippoc al neurogenesis is a critical form of cellular plasticity that is greatly influenced by neural activity. Among the neurotransmitters that are widely implicated in regulating this process are serotonin and norepinephrine, levels of which are modulated by stress, depression and clinical antidepressants. However, studies to date have failed to address a direct role for either neurotransmitter in regulating hippoc al precursor activity. Here we show that norepinephrine but not serotonin directly activates self-renewing and multipotent neural precursors, including stem cells, from the hippoc us of adult mice. Mechanistically, we provide evidence that β 3 -adrenergic receptors, which are preferentially expressed on a Hes5-expressing precursor population in the subgranular zone (SGZ), mediate this norepinephrine-dependent activation. Moreover, intrahippoc al injection of a selective β 3 -adrenergic receptor agonist in vivo increases the number of proliferating cells in the SGZ. Similarly, systemic injection of the β-adrenergic receptor agonist isoproterenol not only results in enhancement of proliferation in the SGZ but also leads to an increase in the percentage of nestin/glial fibrillary acidic protein double-positive neural precursors in vivo . Finally, using a novel ex vivo “slice-sphere” assay that maintains an intact neurogenic niche, we demonstrate that antidepressants that selectively block the reuptake of norepinephrine, but not serotonin, robustly increase hippoc al precursor activity via β-adrenergic receptors. These findings suggest that the activation of neurogenic precursors and stem cells via β 3 -adrenergic receptors could be a potent mechanism to increase neuronal production, providing a putative target for the development of novel antidepressants.
Publisher: Society for Neuroscience
Date: 07-07-2023
DOI: 10.1523/JNEUROSCI.1542-22.2023
Abstract: Activity-dependent changes in the number of AMPA-type glutamate receptors (AMPARs) at the synapse underpin the expression of LTP and LTD, cellular correlates of learning and memory. Post-translational ubiquitination has emerged as a key regulator of the trafficking and surface expression of AMPARs, with ubiquitination of the GluA1 subunit at Lys-868 controlling the post-endocytic sorting of the receptors into the late endosome for degradation, thereby regulating their stability at synapses. However, the physiological significance of GluA1 ubiquitination remains unknown. In this study, we generated mice with a knock-in mutation in the major GluA1 ubiquitination site (K868R) to investigate the role of GluA1 ubiquitination in synaptic plasticity, learning, and memory. Our results reveal that these male mice have normal basal synaptic transmission but exhibit enhanced LTP and deficits in LTD. They also display deficits in short-term spatial memory and cognitive flexibility. These findings underscore the critical roles of GluA1 ubiquitination in bidirectional synaptic plasticity and cognition in male mice. SIGNIFICANCE STATEMENT Subcellular targeting and membrane trafficking determine the precise number of AMPA-type glutamate receptors at synapses, processes that are essential for synaptic plasticity, learning, and memory. Post-translational ubiquitination of the GluA1 subunit marks AMPARs for degradation, but its functional role in vivo remains unknown. Here we demonstrate that the GluA1 ubiquitin-deficient mice exhibit an altered threshold for synaptic plasticity accompanied by deficits in short-term memory and cognitive flexibility. Our findings suggest that activity-dependent ubiquitination of GluA1 fine-tunes the optimal number of synaptic AMPARs required for bidirectional synaptic plasticity and cognition in male mice. Given that increases in amyloid-β cause excessive ubiquitination of GluA1, inhibiting that GluA1 ubiquitination may have the potential to ameliorate amyloid-β-induced synaptic depression in Alzheimer's disease.
Publisher: Wiley
Date: 11-04-2007
DOI: 10.1111/J.1440-1681.2007.04608.X
Abstract: 1. There is mounting evidence that a wide range of antidepressants share the common feature of increasing hippoc al neurogenesis. The specificity of this association has suggested that an ability to increase neurogenesis might be a useful paradigm to screen for compounds with antidepressant activity. 2. The hope of developing better antidepressants has stimulated research into the molecular control of neurogenesis and here we summarize some of the recent findings. We also review recent work that highlights 5-HT7 receptor as a promising molecular target in the treatment of depression. 3. In summary, it appears that 5-HT7 antagonism is capable of producing erse antidepressant-like behavioural effects, alters hippoc al neuronal morphology and synergistically regulates hippoc al neurogenesis.
Publisher: Wiley
Date: 02-08-2017
DOI: 10.1002/DVDY.24545
Abstract: Type 1 adult hippoc al neural stem cells (AH-NSCs) continue to generate neurons throughout life, albeit at a very low rate. The relative quiescence of this population of cells has led to many studies investigating factors that may increase their ision. Current methods of identifying iding AH-NSCs in vivo require the identification and tracing of radial processes back to nuclei within the subgranular zone. However, caveats to this approach include the time-intensive nature of identifying AH-NSCs with such a process, as well as the fact that this approach ignores the relatively more active population of horizontally oriented AH-NSCs that also reside in the subgranular zone. Here we describe, and then verify using Hes5::GFP mice, that labeling for the cell cycle marker Ki67 and selection against the intermediate progenitor cell marker TBR2 (Ki67 These findings provide a simple and accurate way to quantify iding AH-NSCs in vivo using a morphology-independent approach that will facilitate studies into neurogenesis within the hippoc al stem cell niche of the adult brain. Developmental Dynamics 247:194-200, 2018. © 2017 Wiley Periodicals, Inc.
Publisher: Wiley
Date: 09-2020
DOI: 10.1002/DNEU.22729
Abstract: Brain-derived neurotrophic factor (BDNF) signaling plays a major role in the regulation of hippoc al neurogenesis in the adult brain. While the majority of studies suggest that this is due to its effect on the survival and differentiation of newborn neurons, it remains unclear whether this signaling directly regulates neural precursor cell (NPC) activity and which of its two receptors, TrkB or the p75 neurotrophin receptor (p75
Publisher: Society for Neuroscience
Date: 27-05-2015
DOI: 10.1523/JNEUROSCI.0504-15.2015
Abstract: The activity of neural precursor cells in the adult hippoc us is regulated by various stimuli however, whether these stimuli regulate the same or different precursor populations remains unknown. Here, we developed a novel cell-sorting protocol that allows the purification to homogeneity of neurosphere-forming neural precursors from the adult mouse hippoc us and examined the responsiveness of in idual precursors to various stimuli using a clonal assay. We show that within the Hes5-GFP + /Nestin-GFP + /EGFR + cell population, which comprises the majority of neurosphere-forming precursors, there are two distinct subpopulations of quiescent precursor cells, one directly activated by high-KCl depolarization, and the other activated by norepinephrine (NE). We then demonstrate that these two populations are differentially distributed along the septotemporal axis of the hippoc us, and show that the NE-responsive precursors are selectively regulated by GABA, whereas the KCl-responsive precursors are selectively modulated by corticosterone. Finally, based on RNAseq analysis by deep sequencing, we show that the progeny generated by activating NE-responsive versus KCl-responsive quiescent precursors are molecularly different. These results demonstrate that the adult hippoc us contains phenotypically similar but stimulus-specific populations of quiescent precursors, which may give rise to neural progeny with different functional capacity.
Publisher: The Company of Biologists
Date: 05-2004
DOI: 10.1242/DEV.01083
Abstract: Olfactory receptor neurons and the interneurons of the olfactory lobe are organized in distinct units called glomeruli. We have used expression patterns and genetic analysis to demonstrate that a combinatorial code of Roundabout(Robo) receptors act to position sensory terminals within the olfactory lobe. Groups of sensory neurons possess distinct blends of Robo and Robo3 and disruption of levels by loss-of-function or ectopic expression results in aberrant targeting. In the wild type, most of the neurons send collateral branches to the contralateral lobe. Our data suggests that guidance of axons across brain hemispheres is mediated by Slit-dependent Robo2 signaling. The location of sensory arbors at distinct positions within the lobe allows short-range interactions with projection neurons leading to formation of the glomeruli.
Publisher: Wiley
Date: 10-06-2011
DOI: 10.1002/DNEU.20871
Abstract: The regulation of neural precursor cell (NPC) activity is the major determinant of the rate of neuronal production in neurogenic regions of the adult brain. Here, we show that Oncostatin M (Osm) and its receptor, OsmRβ, are both expressed in the subventricular zone (SVZ) and that in contradistinction to leukemia inhibitory factor and ciliary neutrophic factor, Osm directly inhibits the proliferation of adult NPCs as measured by a decreased level of neurosphere formation in vitro. Similarly, intraventricular infusion of Osm dramatically decreases the pool of NPCs in both the SVZ and the hippoc us. In keeping with the inhibitory action of Osm, we reveal that mice lacking OsmRβ have substantially more NPCs in the SVZ, the hippoc us and the olfactory bulb, demonstrating that endogenous Osm signaling is important for NPC homeostasis. Finally, we show that Osm can also inhibit clonal growth of glioblastoma-derived neurospheres, further supporting the close link between NPCs and tumor stem cells.
Publisher: Elsevier BV
Date: 05-2021
Publisher: Elsevier BV
Date: 11-2021
Publisher: Frontiers Media SA
Date: 22-01-2020
Publisher: Springer Science and Business Media LLC
Date: 11-11-2005
Abstract: The development of nervous systems involves reciprocal interactions between neurons and glia. In the Drosophila olfactory system, peripheral glial cells arise from sensory lineages specified by the basic helix-loop-helix transcription factor, Atonal. These glia wrap around the developing olfactory axons early during development and pattern the three distinct fascicles as they exit the antenna. In the moth Manduca sexta , an additional set of central glia migrate to the base of the antennal nerve where axons sort to their glomerular targets. In this work, we have investigated whether similar types of cells exist in the Drosophila antenna. We have used different P(Gal4) lines to drive Green Fluorescent Protein (GFP) in distinct populations of cells within the Drosophila antenna. Mz317::GFP, a marker for cell body and perineural glia, labels the majority of peripheral glia. An additional ~30 glial cells detected by GH146::GFP do not derive from any of the sensory lineages and appear to migrate into the antenna from the brain. Their appearance in the third antennal segment is regulated by normal function of the Epidermal Growth Factor receptor and small GTPases. We denote these distinct populations of cells as Mz317-glia and GH146-glia respectively. In the adult, processes of GH146-glial cells ensheath the olfactory receptor neurons directly, while those of the Mz317-glia form a peripheral layer. Ablation of GH146-glia does not result in any significant effects on the patterning of the olfactory receptor axons. We have demonstrated the presence of at least two distinct populations of glial cells within the Drosophila antenna. GH146-glial cells originate in the brain and migrate to the antenna along the newly formed olfactory axons. The number of cells populating the third segment of the antenna is regulated by signaling through the Epidermal Growth Factor receptor. These glia share several features of the sorting zone cells described in Manduca .
Publisher: Elsevier BV
Date: 10-2000
Publisher: Public Library of Science (PLoS)
Date: 12-06-2014
Publisher: Oxford University Press (OUP)
Date: 22-12-2018
Abstract: The hippoc al dentate gyrus (DG) is a major region of the adult rodent brain in which neurogenesis occurs throughout life. The EphA4 receptor, which regulates neurogenesis and boundary formation in the developing brain, is also expressed in the adult DG, but whether it regulates adult hippoc al neurogenesis is not known. Here, we show that, in the adult mouse brain, EphA4 inhibits hippoc al precursor cell proliferation but does not affect precursor differentiation or survival. Genetic deletion or pharmacological inhibition of EphA4 significantly increased hippoc al precursor proliferation in vivo and in vitro, by blocking EphA4 forward signaling. EphA4 was expressed by mature hippoc al DG neurons but not neural precursor cells, and an EphA4 antagonist, EphA4-Fc, did not activate clonal cultures of precursors until they were co-cultured with non-precursor cells, indicating an indirect effect of EphA4 on the regulation of precursor activity. Supplementation with d-serine blocked the increased precursor proliferation induced by EphA4 inhibition, whereas blocking the interaction between d-serine and N-methyl-d-aspartate receptors (NMDARs) promoted precursor activity, even at the clonal level. Collectively, these findings demonstrate that EphA4 indirectly regulates adult hippoc al precursor proliferation and thus plays a role in neurogenesis via d-serine-regulated NMDAR signaling.
Publisher: Cold Spring Harbor Laboratory
Date: 26-08-2022
DOI: 10.1101/2022.08.25.505357
Abstract: Cholinergic signaling plays a crucial role in the regulation of adult hippoc al neurogenesis and hippoc us-dependent cognitive and mood-related functions. However, the contribution of basal forebrain medial septum (MS) and diagonal band of Broca (DBB) cholinergic neurons that innervate the hippoc us and the identity of the cholinergic receptor(s) that regulate the production and maturation of new neurons are not completely understood. Using a targeted, selective ablation approach, we show that MS/DBB cholinergic neurons support both the survival and morphological maturation of adult-born neurons in the mouse hippoc us. We demonstrate that the muscarinic acetycholine receptor subtype M4 (M4 mAChR) is expressed on a population of quiescent neural precursor cells (NPCs) and that its pharmacological stimulation via intra-hippoc al or systemic administration of M4-selective modulators leads to their activation, thereby enhancing neurogenesis in vivo . Furthermore, we show that the activation of M4 mAChR-expressing quiescent NPCs ameliorates the MS/DBB cholinergic lesion-induced decrease in hippoc al neurogenesis. In contrast, the impairment in the morphological maturation of adult-born neurons due to MS/DBB cholinergic neuron loss is further exacerbated by the systemic administration of an M4-selective allosteric potentiator. These findings reveal novel and stage-specific roles of cholinergic signaling in regulating adult hippoc al neurogenesis. They also uncouple the positive role of selective M4 potentiators in enhancing the production of new neurons from the M4-induced inhibition of their morphological maturation, at least in the context of cholinergic dysfunction. Cholinergic signaling plays an important role in the regulation of adult hippoc al neurogenesis and cognitive function, with impairments in these processes reported as early pathogenic events in age-related dementia. Here, we uncover the presence of cholinergic-responsive hippoc al precursor cells that are are directly activated by selective stimulation of the muscarinic receptor subtype M4. Furthermore, M4-mediated stimulation rescues the decrease in the level of hippoc al neurogenesis following the sepal-hippoc al cholinergic neuron loss. We also reveal that septal-hippoc al cholinergic dysfunction impairs the structural maturation of hippoc al adult-born neurons, an effect which is further exacerbated by M4 receptor modulators. These findings reveal stage-specific roles of cholinergic signaling in regulating functionally relevant adult hippoc al neurogenesis.
Publisher: Wiley
Date: 13-02-2013
DOI: 10.1002/JNR.23199
Abstract: Within the two neurogenic niches of the adult mammalian brain, i.e., the subventricular zone lining the lateral ventricle and the subgranular zone of the hippoc us, there exist distinct populations of proliferating neural precursor cells that differentiate to generate new neurons. Numerous studies have suggested that epigenetic regulation by histone-modifying proteins is important in guiding precursor differentiation during development however, the role of these proteins in regulating neural precursor activity in the adult neurogenic niches remains poorly understood. Here we examine the role of an NAD(+) -dependent histone deacetylase, SIRT1, in modulating the neurogenic potential of neural precursors in the neurogenic niches of the adult mouse brain. We show that SIRT1 is expressed by proliferating adult subventricular zone and hippoc al neural precursors, although its transcript and protein levels are dramatically reduced during neural precursor differentiation. Utilizing a lentiviral-mediated delivery strategy, we demonstrate that abrogation of SIRT1 signaling by RNAi does not affect neural precursor numbers or their proliferation. However, SIRT1 knock down results in a significant increase in neuronal production in both the subventricular zone and the hippoc us. In contrast, enhancing SIRT1 signaling either through lentiviral-mediated SIRT1 overexpression or through use of the SIRT1 chemical activator Resveratrol prevents adult neural precursors from differentiating into neurons. Importantly, knock down of SIRT1 in hippoc al precursors in vivo, either through RNAi or through genetic ablation, promotes their neurogenic potential. These findings highlight SIRT1 signaling as a negative regulator of neuronal differentiation of adult subventricular zone and hippoc al neural precursors. © 2013 Wiley Periodicals, Inc.
Publisher: Elsevier BV
Date: 12-2017
DOI: 10.1016/J.PSYNEUEN.2017.09.003
Abstract: Vitamin D deficiency is prevalent in adults throughout the world. Epidemiological studies have shown significant associations between vitamin D deficiency and an increased risk of various neuropsychiatric and neurodegenerative disorders, such as schizophrenia, depression, Alzheimer's disease and cognitive impairment. However, studies based on observational epidemiology cannot address questions of causality they cannot determine if vitamin D deficiency is a causal factor leading to the adverse health outcome. The main aim of this study was to determine if AVD deficiency would exacerbate the effects of a secondary exposure, in this case social stress, in BALB/c mice and in the more resilient C57BL/6 mice. Ten-week old male BALB/c and C57BL/6 mice were fed a control or vitamin D deficient diet for 10 weeks, and the mice were further separated into one of two groups for social treatment, either Separated (SEP) or Social Defeat (DEF). SEP mice were placed two per cage with a perforated Plexiglas ider, whereas the DEF mice underwent 10days of social defeat prior to behavioural testing. We found that AVD-deficient mice were more vulnerable to the effects of social stress using a social avoidance test, and this was dependent on strain. These results support the hypothesis that vitamin D deficiency may exacerbate behavioural outcomes in mice vulnerable to stress, a finding that can help guide future studies. Importantly, these discoveries support the epidemiological link between vitamin D deficiency and neuropsychiatric and neurodegenerative disorders and has provided clues that can guide future studies related to unravelling the mechanisms of action linking adult vitamin D deficiency and adverse brain related outcomes.
Publisher: Elsevier BV
Date: 05-2011
DOI: 10.1016/J.NEUINT.2011.04.003
Abstract: The generation of new neurons within the dentate gyrus of the mature hippoc us is critical for spatial learning, object recognition and memory, whereas new neurons born in the subventricular zone (SVZ) contribute to olfactory function. Adult neurogenesis is a multistep process that begins with the activation and proliferation of a pool of stem recursor cells. Although the presence of self-renewing and multipotent neural precursors is well established in the SVZ, it is only recently that the existence of such a precursor population has been demonstrated in the hippoc us, the region of the brain involved in learning and memory. Determining how this normally latent pool can be activated therefore offers considerable potential for the development of targeted neurogenic-based therapeutics to ameliorate the cognitive decline associated with hippoc al dysfunction in several neurodegenerative diseases. In this review, we summarize the effects of neural activity, various molecular factors and pharmaceutical agents, as well as voluntary exercise, in activating endogenous neural precursors in the two neurogenic niches of the adult brain, and highlight the role of activation-driven enhancement of neurogenesis for the treatment of psychiatric illness and aging dementia.
Publisher: Springer Science and Business Media LLC
Date: 16-07-2022
DOI: 10.1038/S41539-022-00133-Y
Abstract: Adult hippoc al neurogenesis in the developmental process of generating and integrating new neurons in the hippoc us during adulthood and is a unique form of structural plasticity with enormous potential to modulate neural circuit function and behaviour. Dysregulation of this process is strongly linked to stress-related neuropsychiatric conditions such as anxiety and depression, and efforts have focused on unravelling the contribution of adult-born neurons in regulating stress response and recovery. Chronic stress has been shown to impair this process, whereas treatment with clinical antidepressants was found to enhance the production of new neurons in the hippoc us. However, the precise role of adult hippoc al neurogenesis in mediating the behavioural response to chronic stress is not clear and whether these adult-born neurons buffer or increase susceptibility to stress-induced mood-related maladaptation remains one of the controversial issues. In this review, we appraise evidence probing the causal role of adult hippoc al neurogenesis in the regulation of emotional behaviour in rodents. We find that the relationship between adult-born hippoc al neurons and stress-related mood disorders is not linear, and that simple subtraction or addition of these neurons alone is not sufficient to lead to anxiety/depression or have antidepressant-like effects. We propose that future studies examining how stress affects unique properties of adult-born neurons, such as the excitability and the pattern of connectivity during their critical period of maturation will provide a deeper understanding of the mechanisms by which these neurons contribute to functional outcomes in stress-related mood disorders.
Publisher: Society for Neuroscience
Date: 20-01-2010
DOI: 10.1523/JNEUROSCI.2309-09.2010
Abstract: Slow-onset adaptive changes that arise from sustained antidepressant treatment, such as enhanced adult hippoc al neurogenesis and increased trophic factor expression, play a key role in the behavioral effects of antidepressants. α 2 -Adrenoceptors contribute to the modulation of mood and are potential targets for the development of faster acting antidepressants. We investigated the influence of α 2 -adrenoceptors on adult hippoc al neurogenesis. Our results indicate that α 2 -adrenoceptor agonists, clonidine and guanabenz, decrease adult hippoc al neurogenesis through a selective effect on the proliferation, but not the survival or differentiation, of progenitors. These effects persist in dopamine β-hydroxylase knock-out ( Dbh −/− ) mice lacking norepinephrine, supporting a role for α 2 -heteroceptors on progenitor cells, rather than α 2 -autoreceptors on noradrenergic neurons that inhibit norepinephrine release. Adult hippoc al progenitors in vitro express all the α 2 -adrenoceptor subtypes, and decreased neurosphere frequency and BrdU incorporation indicate direct effects of α 2 -adrenoceptor stimulation on progenitors. Furthermore, coadministration of the α 2 -adrenoceptor antagonist yohimbine with the antidepressant imipramine significantly accelerates effects on hippoc al progenitor proliferation, the morphological maturation of newborn neurons, and the increase in expression of brain derived neurotrophic factor and vascular endothelial growth factor implicated in the neurogenic and behavioral effects of antidepressants. Finally, short-duration (7 d) yohimbine and imipramine treatment results in robust behavioral responses in the novelty suppressed feeding test, which normally requires 3 weeks of treatment with classical antidepressants. Our results demonstrate that α 2 -adrenoceptors, expressed by progenitor cells, decrease adult hippoc al neurogenesis, while their blockade speeds up antidepressant action, highlighting their importance as targets for faster acting antidepressants.
Publisher: Elsevier BV
Date: 05-2021
Publisher: The Company of Biologists
Date: 2020
DOI: 10.1242/BIO.053132
Abstract: Sulfate is a key anion that is required for a range of physiological functions within the brain. These include sulfonation of extracellular proteoglycans to facilitate local growth factor binding and to regulate the shape of morphogen gradients during development. We have previously shown that mice lacking one allele of the sulfate transporter Slc13a4 exhibit reduced sulfate transport into the brain, deficits in social behaviour, reduced performance in learning and memory tasks, and abnormal neurogenesis within the ventricular/subventricular zone lining the lateral ventricles. However, whether these mice have deficits in hippoc al neurogenesis was not addressed. Here, we demonstrate that adult Slc13a4+/- mice have increased neurogenesis within the subgranular zone (SGZ) of the hippoc al dentate gyrus, with elevated numbers of neural progenitor cells and intermediate progenitors. In contrast, by 12 months of age there were reduced numbers of neural stem cells in the SGZ of heterozygous mice. Importantly, we did not observe any changes in proliferation when we isolated and cultured progenitors in vitro in neurosphere assays, suggestive of a cell-extrinsic requirement for sulfate in regulating hippoc al neurogenesis. Collectively, these data demonstrate a requirement for sulfate transport during postnatal brain development to ensure normal adult hippoc al neurogenesis.
Publisher: Humana Press
Date: 2013
DOI: 10.1007/978-1-62703-574-3_4
Abstract: It is now well established that a resident population of neural precursor cells continues to generate new neurons in the adult hippoc us throughout life. Numerous studies have suggested that these newborn neurons preferentially participate in the functional hippoc al circuitry that leads to enhancement of learning, cognition and mood. Therefore, understanding the molecular mechanisms that regulate the activity of these endogenous precursor cells is paramount to develop novel regenerative strategies for the treatment of neurological and psychiatric disorders. The neurosphere assay has been instrumental in discovering the presence of stem and precursor cell population from several brain regions. In this chapter, we describe this assay to specifically isolate and culture neural stem and precursor cell populations from the adult hippoc us of mice. In addition, we provide methods to conduct detailed assays to examine their functional properties such as proliferation, self-renewal, and differentiation.
Start Date: 07-2011
End Date: 12-2019
Amount: $21,000,000.00
Funder: Australian Research Council
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