A5056582943- Neurogenesis and neuroplasticity mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Epigenetics and DNA Methylation
- Cytokine Signaling Pathways and Interactions
- Bone Metabolism and Diseases
- Nerve injury and regeneration
- MicroRNA in disease regulation
- Neonatal Respiratory Health Research
- RNA Interference and Gene Delivery
- Axon Guidance and Neuronal Signaling
- Immune cells in cancer
- Multiple Sclerosis Research Studies
- interferon and immune responses
- Histone Deacetylase Inhibitors Research
- Immune Response and Inflammation
- Reproductive System and Pregnancy
- Bone health and treatments
- Genetics and Neurodevelopmental Disorders
- Chemokine receptors and signaling
- RNA and protein synthesis mechanisms
- Glioma Diagnosis and Treatment
- Neuroscience and Neuropharmacology Research
- CRISPR and Genetic Engineering
- Circular RNAs in diseases
- Garlic and Onion Studies
National Institute of Mental Health
2023-2024
Australian Regenerative Medicine Institute
2012-2024
Monash University
2004-2024
National Institutes of Health
2024
Chinese University of Hong Kong
2021
Florey Institute of Neuroscience and Mental Health
2006-2018
The University of Melbourne
2006-2018
Walter and Eliza Hall Institute of Medical Research
2004-2010
Parks Victoria
2001
The University of Queensland
2001
Mounting evidence suggests that neuronal activity influences myelination, potentially allowing for experience-driven modulation of neural circuitry. The degree to which is capable regulating myelination at the individual axon level unclear. Here we demonstrate stimulation somatosensory axons in mouse brain increases proliferation and differentiation oligodendrocyte progenitor cells (OPCs) within underlying white matter. Stimulated display an increased probability being myelinated compared...
Parenchymal oligodendrocyte progenitor cells (pOPCs) are considered the principal cell type responsible for oligodendrogenesis and remyelinaton in demyelinating diseases. Recent studies have demonstrated that neural precursor (NPCs) from adult subventricular zone (SVZ) can also generate new oligodendrocytes after demyelination. However, relative contribution of NPCs versus pOPCs to remyelination is unknown. We used vivo genetic fate mapping assess behavior each within corpus callosi (CCs)...
A mechanistic connection between aging and development is largely unexplored. Through profiling age-related chromatin transcriptional changes across 22 murine cell types, analyzed alongside previous mouse human organismal maturation datasets, we uncovered a transcription factor binding site (TFBS) signature common to both processes. Early-life candidate cis-regulatory elements (cCREs), progressively losing accessibility during aging, are enriched for cell-type identity TFBSs. Conversely,...
Although our understanding of adult neurogenesis has increased dramatically over the last decade, confusion still exists regarding both identity stem cell responsible for neuron production and mechanisms that regulate its activity. Here we show, using flow cytometry, a small population cells (0.3%) within niche rat subventricular zone (SVZ) expresses p75 neurotrophin receptor (p75 NTR ) these are in newborn animals. In adult, -positive contains all neurosphere-producing precursor cells,...
The critical role of oligodendrocytes in producing and maintaining myelin that supports rapid axonal conduction CNS neurons is well established. More recently, additional roles for have been posited, including provision trophic factors metabolic support neurons. To investigate the functional consequences oligodendrocyte loss, we generated a transgenic mouse model conditional ablation. In this model, are rendered selectively sensitive to exogenously administered diphtheria toxin (DT) by...
The adult mammalian brain maintains populations of neural stem cells within discrete proliferative zones. Understanding the molecular mechanisms regulating cell function is limited. Here, we show that MYST family histone acetyltransferase Querkopf (Qkf, Myst4, Morf)-deficient mice have cumulative defects in neurogenesis vivo, resulting declining numbers olfactory bulb interneurons, a population neurons produced large during adulthood. Qkf-deficient fewer and migrating neuroblasts rostral...
Nanodiamonds (NDs) containing silicon vacancy (SiV) defects were evaluated as a potential biomarker for the labeling and fluorescent imaging of neural precursor cells (NPCs). SiV-containing NDs synthesized using chemical vapor deposition ion implantation. Spectrally, exhibited extremely stable fluorescence narrow bandwidth emission with an excellent signal to noise ratio exceeding that nitrogen-vacancy (NV) centers. NPCs labeled normal cell viability proliferative properties consistent...
People with Down syndrome (DS) exhibit abnormal brain structure. Alterations affecting neurotransmission and signalling pathways that govern function are also evident. A large number of genes simultaneously expressed at levels in DS; therefore, it is a challenge to determine which gene(s) contribute specific abnormalities, then identify the key molecular involved. We generated RCAN1-TG mice study consequences RCAN1 over-expression investigate contribution phenotype DS. structural...
The adult subventricular zone (SVZ) is a potential source of precursor cells to replace neural lost during demyelination. To better understand the molecular events that regulate cell responsiveness in this context we undertook microarray and quantitative PCR based analysis genes expressed within SVZ cuprizone-induced We identified an up-regulation encoding bone morphogenic protein 4 (BMP4) its receptors. Immunohistochemistry confirmed increase BMP4 levels also showed phosphorylated SMAD...
Approaches to investigate adult oligodendrocyte progenitor cells (OPCs) by targeted cell ablation in the rodent CNS have limitations extent and duration of OPC depletion. We developed a pharmacogenetic approach for conditional ablation, eliminating >98% OPCs throughout brain. By combining recombinase-based transgenic viral strategies targeting ventricular-subventricular zone (V-SVZ)-derived neural precursor (NPCs), we found that new PDGFRA-expressing born V-SVZ repopulated OPC-deficient...
Enhancement of oligodendrocyte survival through activation leukemia inhibitory factor receptor (LIFR) signaling is a candidate therapeutic strategy for demyelinating disease. However, in other cell types, LIFR under tight negative regulation by the intracellular protein suppressor cytokine 3 (SOCS3). We, therefore, postulated that deletion SOCS3 gene oligodendrocytes would promote beneficial effects limiting demyelination. By studying wild-type and LIF-knockout mice, we established...
Background Down syndrome (DS) individuals suffer mental retardation with further cognitive decline and early onset Alzheimer's disease. Methodology/Principal Findings To understand how trisomy 21 causes these neurological abnormalities we investigated changes in gene expression networks combined a systematic cell lineage analysis of adult neurogenesis using the Ts1Cje mouse model DS. We demonstrated down regulation number key genes involved proliferation cycle progression including Mcm7,...
Aims: Hypoxic-ischaemic encephalopathy (HIE) is one of the most serious complications in neonates and infants.Mesenchymal stromal cell (MSC)-based therapy emerging as a promising treatment avenue for HIE.However, despite its enormous potential, clinical application MSCs limited by heterogeneity, low isolation efficiency unpredictable effectiveness.In this study, we examined therapeutic effects underlying mechanisms human pluripotent stem cell-derived ectomesenchymal cells (hPSC-EMSCs) rat...
SOCS7 is a member of the suppressor cytokine signaling (SOCS) family proteins (SOCS1-SOCS7 and CIS). SOCS are composed an N-terminal domain variable length, central Src homology 2 domain, C-terminal box. Biochemical genetic studies have revealed that SOCS1, SOCS2, SOCS3, CIS play important role in termination growth factor signaling. However, biological actions other less well defined. To investigate physiological SOCS7, we used gene targeting to generate mice lack expression Socs7 gene. -/-...
Neural stem cells, which are confined in localised niches unable to repair large brain lesions because of an inability migrate long distances and engraft. To overcome these problems, previous research has demonstrated the use biomaterial implants redirect increased numbers endogenous neural cell populations. However, fate diverted cells their progeny remains unknown. Here we show that originating from subventricular zone can cortex with aid a long-lasting injectable hydrogel within mouse...
Abstract The identification of factors that regulate myelination provides important insight into the molecular mechanisms coordinate nervous system development and myelin regeneration after injury. In this study, we investigated role amyloid precursor protein (APP) its paralogue precursor‐like 2 (APLP2) in using APP APLP2 knockout (KO) mice. Given BACE1 regulates sheath thickness both peripheral central systems, sought to determine if APLP2, as alternate substrates, also modulate...
Astrocytes play critical roles after brain injury, but their precise function is poorly defined. Utilizing single-nuclei transcriptomics to characterize astrocytes ischemic stroke in the visual cortex of marmoset monkey, we observed nearly complete segregation between and control astrocyte clusters. Screening for top 30 differentially expressed genes that might limit recovery, discovered a majority RTN4A/ NogoA, neurite-outgrowth inhibitory protein previously only associated with...
The postnatal neocortex has traditionally been considered a non-neurogenic region, under non-pathological conditions. A few studies suggest, however, that small subpopulation of neural cells born during life can differentiate into neurons take up residence within the neocortex, implying neurogenesis could occur in this albeit at low level. Evidence to support hypothesis remains controversial while source putative progenitors responsible for generating new is unknown. Here we report...