Elizabeth J Coulson

Elizabeth J Coulson
The University of Queensland | UQ · Queensland Brain Institute and School of Biomedical Sciences

PhD

About

126
Publications
10,840
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
3,552
Citations
Introduction
My lab is currently focusing on the reasons why cholinergic neurons of the basal forebrain die in Alzheimer’s disease, what contribution their loss makes to cognitive decline and whether manipulating neurotrophic signalling (NGF, BDNF, TrkA/B, p75) can protect or restore cognitive function, and what role the neurotrophins play in the normal function of these neurons.

Publications

Publications (126)
Article
Full-text available
The use of animals as models of human physiology is, and has been for many years, an indispensable tool for understanding the mechanisms of human disease. In Parkinson’s disease, various mouse models form the cornerstone of these investigations. Early models were developed to reflect the traditional histological features and motor symptoms of Parki...
Preprint
Full-text available
Cholinergic signaling plays a crucial role in the regulation of adult hippocampal neurogenesis and hippocampus-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 hippocampus and the identity of the cholinergic recepto...
Article
Frailty, a state of reduced physiological reserve, has not been studied in consumers with treatment-resistant schizophrenia, despite known elevated rates of comorbidity and psychosocial impairment. This study applies a frailty index to the electronic medical records of 78 adults with treatment-resistant schizophrenia, aged 18-64 years, to determine...
Article
Degeneration of cholinergic neurons in the basal forebrain (BF) contributes to cognitive impairment in Alzheimer's disease (AD) and other disorders. Atrophy of BF volume measured by structural MRI is thought to represent the loss of cholinergic neurons in this structure. As there are multiple types of neurons in the BF as well as glia and axons, wh...
Article
Full-text available
Dysfunction of the cholinergic basal forebrain (BF) neurotransmitter system, including cholinergic axon denervation of the cortex, plays an important role in cognitive decline and dementia. A validated method to directly quantify cortical cholinergic terminal integrity enables exploration of the involvement of this system in diverse cognitive profi...
Article
Full-text available
Inappropriate expansion of antibody-secreting cells (ASCs) is typical of systemic lupus erythematosus (SLE), but the regulatory signaling of pathogenic ASCs is unclear. The present study shows that brain-derived neurotrophic factor precursor (proBDNF) and its high-affinity pan-75 neurotrophin receptor (p75NTR) are highly expressed in CD19+CD27hiCD3...
Article
Full-text available
Neurotrophin signalling is essential for normal nervous system development and adult function. Neurotrophins are secreted proteins that signal via interacting with two neurotrophin receptor types: the multifaceted p75 neurotrophin receptor (p75) and the tropomyosin receptor kinase (Trk) receptors. In vivo, neurons compete for the limited quantities...
Article
Objective Emerging evidence suggests that people with severe mental illness (SMI) have an increased risk of frailty. We conducted a systematic review to investigate the prevalence and correlates of frailty, as well as the efficacy of frailty interventions, in this population. Methods We searched databases from inception to 21 September 2021 for st...
Article
Full-text available
Aims Obstructive sleep apnoea (OSA) occurs with greater frequency in advancing age. The resulting sleep fragmentation and oxygen desaturations may induce or contribute to neurodegeneration. As such, OSA may be an important modifiable risk factor for the development of dementia. However, the prevalence of OSA within the population with cognitive imp...
Article
Full-text available
Introduction Obstructive sleep apnoea (OSA) is a risk factor for cognitive impairment and has been associated with deficits in executive function, attention, and memory. Potential mechanisms of harm include sleep disruption and intermittent hypoxaemia. Our aim was to investigate whether the apnoea-hypopnoea index (AHI), arousal index (AI) and mean...
Article
Cholinergic basal forebrain (cBF) neurons are particularly vulnerable to degeneration following trauma and in neurodegenerative conditions. One reason for this is their characteristic expression of the p75 neurotrophin receptor (p75NTR), which is upregulated and mediates neuronal death in a range of neurological and neurodegenerative conditions, in...
Article
The mechanism by which antidepressants elicit clinical improvements has proven elusive. In a recent publication in Cell, Casarotto et al. (2021) reveal a surprising direct interaction between antidepressants and TrkB. This link provides an important mechanistic insight into synaptic remodeling that may assist in the design of improved antidepressan...
Article
The production and circuit integration of new neurons is one of the defining features of the adult mammalian hippocampus. A wealth of evidence has established that adult hippocampal neurogenesis is exquisitely sensitive to neuronal activity-mediated regulation. How these signals are interpreted and contribute to neurogenesis and hippocampal functio...
Article
Full-text available
Major depression is a prevalent and long-lasting psychiatric illness with severe functional impairment and high suicide rate. We have previously shown that the ventrolateral orbital cortex (VLO) plays a key role in the stress responses in mice, but the underlying mechanisms remains unclear. Here, we used proteomic method to identify differentially...
Article
Degeneration of cholinergic basal forebrain (BF) neurons play a role in the progression of Alzheimer’s disease (AD), with atrophy of the BF preceding cognitive dysfunction. Here, we investigated whether the presence of Ab and/or Tau PET tracer retention in cognitively normal elderly controls was associated with BF atrophy. Cognitively healthy parti...
Article
Full-text available
The blood brain barrier (BBB) and blood spinal cord barrier (BSCB) are highly specialised structures that limit molecule entry from the blood and maintain homeostasis within the central nervous system (CNS). BBB and BSCB breakdown are associated with multiple neurodegenerative diseases. Given the key role of neuroprotective barrier impairment in ne...
Article
Full-text available
The p75 neurotrophin receptor (p75NTR) is required for maintaining peripheral sensory neuron survival and function; however, the underlying cellular mechanism remains unclear. The general view is that expression of p75NTR by the neuron itself is required for maintaining sensory neuron survival and myelination in the peripheral nervous system (PNS)....
Article
In Alzheimer’s disease (AD)glial fibrillary acidic protein (GFAP) is expressed by reactive astrocytessurroundingβ‐amyloid (Aβ) plaques, whereasbrain‐derived neurotrophic factor (BDNF) levels are typically reduced. We compared the expression of GFAP, BDNF, and its precursor proBDNF in the dorsal hippocampus of two transgenicAD mouse models.APPSwe YA...
Preprint
Full-text available
Epidemiological studies indicate that obstructive sleep apnoea is a strong risk factor for the development of Alzheimer's disease but the mechanisms of the risk remain unclear. We developed a method of modelling obstructive sleep apnoea in mice that replicates key features of human obstructive sleep apnoea: altered breathing during sleep, sleep dis...
Preprint
The blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB) are highly specialised structures that limit molecule entry from the blood, and maintain homeostasis within the central nervous system (CNS). BBB and BSCB breakdown are associated with multiple neurodegenerative diseases. Given the key role of neuroprotective barrier impairment in n...
Article
Brain‐derived neurotrophic factor signaling plays a major role in the regulation of hippocampal 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) activit...
Article
During development, the p75 neurotrophin receptor (p75NTR) is widely expressed in the nervous system where it regulates neuronal differentiation, migration and axonal outgrowth. p75NTR also mediates the survival and death of newly born neurons, with functional outcomes being dependent on both timing and cellular context. Here, we show that knockout...
Article
Full-text available
Alzheimer's disease (AD) is associated with the cleavage of the amyloid precursor protein (APP) to produce the toxic amyloid-β (Aβ) peptide. Accumulation of Aβ, together with the concomitant inflammatory response, ultimately leads to neuronal death and cognitive decline. Despite AD progression underpinned by both neuronal and immunological componen...
Article
Full-text available
The degeneration of cholinergic basal forebrain (cBF) neurons in Alzheimer’s disease (AD) leads to the cognitive impairment associated with this condition. cBF neurons express the p75 neurotrophin receptor (p75NTR), which mediates cell death, and the extracellular domain of p75NTR can bind to amyloid beta (Aβ) and promote its degradation. Here, we...
Article
Full-text available
Schwann cell reprogramming and differentiation are crucial prerequisites for neuronal regeneration and re-myelination to occur following injury to peripheral nerves. The neurotrophin receptor p75NTR has been identified as a positive modulator for Schwann cell myelination during development and implicated in promoting nerve regeneration after injury...
Article
There is in vitro evidence that sorting nexin family member 27 (SNX27), a member of the retromer complex, changes the distribution of the amyloid-beta (Aβ) precursor protein (APP) to promote its recycling and thereby prevent the production of Aβ, the toxic protein associated with Alzheimer's disease (AD). In this study, we analyzed the phenotype of...
Article
Full-text available
Cholinergic basal forebrain neurons are defined by their expression of the p75 neurotrophin receptor (p75NTR) and Trk neurotrophin receptors in addition to cholinergic markers. It is known that the neurotrophins, particularly nerve growth factor, mediate cholinergic neuronal development and maintenance. However, the role of neurotrophin signalling...
Article
Full-text available
Cholinergic basal forebrain (cBF)-derived neurotransmission plays a crucial role in regulating neuronal function throughout the cortex, yet the mechanisms controlling cholinergic innervation to downstream targets have not been elucidated. Here we report that removing the p75 neurotrophin receptor (p75NTR) from cBF neurons induces a significant impa...
Article
Full-text available
Degeneration of basal forebrain cholinergic neurons (BFCNs) precedes hippocampal degeneration and pathological amyloid-beta (Aβ) accumulation, and underpins the development of cognitive dysfunction in sporadic Alzheimer’s disease (AD). We hypothesized that degeneration of BFCNs causes a decrease in neurotrophin levels in innervated brain areas, whi...
Article
Full-text available
Alzheimer's disease is characterized by cognitive decline, neuronal degeneration, and the accumulation of amyloid-beta (Aβ). Although, the neurotoxic Aβ peptide is widely believed to trigger neuronal dysfunction and degeneration in Alzheimer's disease, the mechanism by which this occurs is poorly defined. Here we describe a novel, Aβ-triggered apop...
Article
Read the highlighted article 'Exercise and BDNF reduce Aβ production by enhancing α-secretase processing of APP' on page doi: 10.1111/jnc.14034.
Article
Programmed cell death or apoptosis is a genetically based mechanism that has evolved to eliminate superfluous cells. Upon activation of the extrinsic apoptotic pathway, an extracellular apoptotic signal is transmitted to the cytosol via transmembrane death receptors (DRs) of the tumor necrosis factor receptor superfamily. The apoptotic signal emana...
Article
Full-text available
Nature Communications 7 : Article number: 12976 doi: 10.1038/ncomms12976 ( 2016 ); Published: 30 September 2016 ; Updated: 23 November 2016 In Fig. 3 of this Article, an image attribution was inadvertently omitted.
Article
Alzheimer's disease (AD) is a progressive, irreversible neurodegenerative disease that destroys memory and cognitive function. Aggregates of hyperphosphorylated tau protein are a prominent feature in the brain of patients with AD, and are a major contributor to neuronal toxicity and disease progression. However, the factors that initiate the toxic...
Article
Full-text available
Axonal retrograde transport of signalling endosomes from the nerve terminal to the soma underpins survival. As each signalling endosome carries a quantal amount of activated receptors, we hypothesized that it is the frequency of endosomes reaching the soma that determines the scale of the trophic signal. Here we show that upregulating synaptic acti...
Data
Retrograde flux of CTB carriers in stimulated neurons
Data
Retrograde flux of CTB carriers in stimulated neurons pretreated with ANA-12
Data
Retrograde flux of CTB carriers in resting neurons
Data
Retrograde flux of CTB carriers in stimulated neurons pretreated with K252a
Data
p75 Neurotrophin Receptor Expression Defines a Population of BDNF-Responsive Neurogenic Precursor Cells
Article
The neurotrophin receptor (p75(NTR)) can mediate neuronal apoptosis in disease or following trauma, and facilitate survival through interactions with Trk receptors. Here we tested the ability of a p75(NTR)-derived trophic cell-permeable peptide, c29, to inhibit p75(NTR)-mediated motor neuron death. Acute c29 application to axotomized motor neuron a...
Article
Full-text available
The basal forebrain degenerates in Alzheimer's disease (AD) and this process is believed to contribute to the cognitive decline observed in AD patients. Impairment in spatial navigation is an early feature of the disease but whether basal forebrain dysfunction in AD is responsible for the impaired navigation skills of AD patients is not known. Our...
Article
This Editorial highlights a study by Hermey and colleagues in the current issue of Journal of Neurochemistry. In their study, the authors provide novel insights into single-nucleotide polymorphisms associated with Alzheimer's disease and linked to the SorCS1 gene, toward a better understanding of the interaction of sorting receptor proteins which p...
Article
Full-text available
The brains of patients suffering from Alzheimer’s disease (AD) have three classical pathological hallmarks: amyloid-beta (Aβ) plaques, tau tangles, and neurodegeneration, including that of cholinergic neurons of the basal forebrain. However the relationship between Aβ burden and basal forebrain degeneration has not been extensively studied. To inve...
Article
Full-text available
The role of the p75 neurotrophin receptor (p75NTR) in adult cholinergic basal forebrain (cBF) neurons is unclear due to conflicting results from previous studies and to limitations of existing p75NTR-knock-out mouse models. In the present study we used a novel conditional knock-out line (ChAT-cre p75in/in) to assess the role of p75NTR in the cBF by...
Article
Evaluation of the efficacy of novel therapeutics for potential treatment of Alzheimer's Disease (AD) requires an animal model that develops age{\hyphen}related cognitive deficits reproducibly between independent groups of investigators. Herein, we assessed comparative temporal changes in spatial memory function in two commercially available transge...
Article
Neurotrophins play a critical role in neuronal development and survival, as well as maintenance of the adult nervous system. Neurotrophins can mediate their effects by signalling locally at the nerve terminal, or signalling retrogradely from the axonal terminal to the cell soma to regulate gene expression. Given that the axon terminals of many nerv...
Article
Full-text available
Read the full article Botulinum protease-cleaved snare fragments induce cytotoxicity in neuroblastoma cells' on page .
Article
Full-text available
Older age is associated with changes in the brain, including the medial temporal lobe, which may result in mild spatial navigation deficits, especially in allocentric navigation. The aim of the study was to characterize the profile of real-space allocentric (world-centered, hippocampus dependent) and egocentric (body-centered, parietal lobe depende...
Article
Full-text available
Background: Drug development for Alzheimer disease (AD) is challenged by the success in animal models tested in the Morris water maze (MWM) and the subsequent failures to meet primary outcome measures in phase II or III clinical trials in patients. The human variant of MWM (hMWM) enables us to examine allocentric and egocentric navigation as in th...
Article
Read the full article Amyloid beta(1-42) (A(42)) up- regulates the expression of sortilin via the p75(NTR)/RhoA signaling pathway' on doi:
Article
Full-text available
The lipid phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P 2), synthesised by PIKfyve, regulates a number of intracellular membrane trafficking pathways. Genetic alteration of the PIKfyve complex, leading to even a mild reduction in PtdIns(3,5)P 2, results in marked neurodegeneration via an uncharacterised mechanism. In the present study we have...
Data
Vacuolation and cell death in glial cells. (A) Still images of glial cells within the neuron preparation treated with 1 µM YM-201636 for the times shown and imaged by phase contrast. (B) Percentage of dead glial cells, n = 4. (C) Percentage of vacuolated glial cells, n = 4. All results show mean ± SEM. Circle = DMSO, square = YM-201636. Significanc...
Data
Increased LC3 levels in YM-201636-treated neurons. (A) Immunoblotting for LC3 and ß-actin in primary hippocampal neurons treated with DMSO or 1 µM YM-201636 for 4 h or 22 h, or maintained in serum-free medium (Starved) for 4 h. (B) The level of LC3-II was normalised to total LC3 and quantified for each time point relative to the control treatment,...
Data
Morphological classification of vacuoles and autophagic/lysosomal compartments. Primary hippocampal neurons were treated with 1 µM YM-201636 for 4 h, fixed and processed for electron microscopy. Autophagosomes presenting a double membrane and luminal content indistinguishable from cytosol were classified as immature (AVi), whereas autophagic compar...
Data
Time-lapse imaging of primary hippocampal neurons – control. Cultured hippocampal neurons were grown for 2 days in a 24-well plate before imaging with an inverted Axio Observer microscope and AxioVision software (Zeiss). The neurons were contained in a 37°C, 5% CO2 chamber during time-lapse imaging. DMSO was added at 0 min (immediately following fr...
Data
Time-lapse imaging of primary hippocampal neurons –1 µM YM-201636. Cultured hippocampal neurons were grown for 2 days in a 24-well plate before imaging with an inverted Axio Observer microscope and AxioVision software (Zeiss). The neurons were contained in a 37°C, 5% CO2 chamber during time-lapse imaging. YM-201636 (1 µM) was added at 0 min (immedi...
Article
Full-text available
Facilitation of nerve growth factor (NGF) signaling by the p75 neurotrophin receptor (p75NTR) is critical for neuronal survival and differentiation. However, the interaction between p75NTR and TrkA receptors required for this activity is not understood. Here we report that a specific 29 amino acid peptide derived from the intracellular-domain fragm...