Mariana Vargas-Caballero

Mariana Vargas-Caballero
University of Southampton · Faculty of Natural and Environmental Sciences

PhD in Neuroscience

About

47
Publications
9,172
Reads
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1,487
Citations
Citations since 2017
23 Research Items
850 Citations
2017201820192020202120222023050100150
2017201820192020202120222023050100150
2017201820192020202120222023050100150
2017201820192020202120222023050100150
Additional affiliations
November 2012 - present
University of Southampton
Position
  • Lecturer
October 2007 - October 2012
University of Oxford
Position
  • PostDoc Position

Publications

Publications (47)
Article
Full-text available
Tau becomes abnormally hyper-phosphorylated and aggregated in tauopathies like Alzheimers disease (AD). As age is the greatest risk factor for developing AD, it is important to understand how tau protein itself, and the pathways implicated in its turnover, change during aging. We investigated age-related changes in total and phosphorylated tau in b...
Preprint
Full-text available
During subarachnoid haemorrhage, a blood clot forms in the subarachnoid space releasing extracellular haemoglobin (Hb), which causes oxidative damage and cell death in surrounding tissues. High rates of disability and cognitive decline in SAH survivors is attributed to loss of neurons and functional connections during secondary brain injury. Haptog...
Article
Full-text available
Amyloid-beta (Aβ) and tau protein are both involved in the pathogenesis of Alzheimer’s disease. Aβ produces synaptic deficits in wild-type mice that are not seen in Mapt−/− mice, suggesting that tau protein is required for these effects of Aβ. However, whether some synapses are more selectively affected and what factors may determine synaptic vulne...
Article
Full-text available
Alzheimer’s disease is linked to increased levels of amyloid beta (Aβ) in the brain, but the mechanisms underlying neuronal dysfunction and neurodegeneration remain enigmatic. Here, we investigate whether organizational characteristics of functional presynaptic vesicle pools, key determinants of information transmission in the central nervous syste...
Article
Full-text available
Cognitive dysfunction in Alzheimer’s disease (AD) is caused by disturbances in neuronal circuits of the brain underpinned by synapse loss, neuronal dysfunction and neuronal death. Amyloid beta and tau protein cause these pathological changes and enhance neuroinflammation, which in turn modifies disease progression and severity. Vagal nerve stimulat...
Preprint
Tau becomes abnormally hyper-phosphorylated and aggregated in tauopathies like Alzheimers disease (AD). As age is the greatest risk factor for developing AD, it is important to understand how tau protein itself, and the pathways implicated in its turnover, change during aging. We investigated age-related changes in total and phosphorylated tau in b...
Article
Full-text available
Background Multimerization is a key process in prion-like disorders such as Alzheimer’s disease (AD), since it is a requirement for self-templating tau and beta-amyloid amyloidogenesis. AT8-immunohistochemistry for hyperphosphorylated tau is currently used for the diagnosis and staging of tau pathology. Given that tau–tau interactions can occur in...
Article
Full-text available
RNA G-quadruplexes (G4s) are secondary structures proposed to function as regulators of post-transcriptional mRNA localisation and translation. G4s within some neuronal mRNAs are known to control distal localisation and local translation, contributing to distinct local proteomes that facilitate the synaptic remodelling attributed to normal cellular...
Article
The deposition of misfolded, aggregated tau protein is a hallmark of several neurodegenerative diseases, collectively termed “tauopathies”. Tau pathology spreads throughout the brain along connected pathways in a prion-like manner. The process of tau pathology propagation across circuits is a focus of intense research and has been investigated in v...
Article
The molecular processes underlying the aging-related decline in cognitive performance and memory observed in humans are poorly understood. Studies in rodents have shown a decrease in N-methyl-D-aspartate receptors (NMDARs) that contain the GluN2B subunit in aging synapses, and this decrease is correlated with impaired memory functions. However, the...
Preprint
Full-text available
The molecular processes underlying the ageing-related decline in cognitive performance and memory observed in humans are poorly understood. Studies in rodents have shown that N-methyl-D-aspartate receptors (NMDARs) containing GluN2B subunits can enhance the ability of synapses to undergo long term potentiation. In ageing rodents, the contribution o...
Article
Full-text available
Glutamate receptors of the N-methyl-D-aspartate (NMDA) family are coincident detectors of pre- and postsynaptic activity, allowing Ca2+ influx into neurons. These properties are central to neurological disease mechanisms and are proposed to be the basis of associative learning and memory. In addition to the well-characterised canonical GluN2A NMDAR...
Preprint
Full-text available
RNA G-quadruplexes (G4s) are non-canonical secondary structures that have been proposed to function as regulators of post-transcriptional mRNA localisation and translation. G4s within 3' UTRs of some neuronal mRNAs are known to control their distal localisation and local translation, contributing to the distinct local proteomes that facilitate the...
Article
Abstract Neurofibrillary tangles, formed of misfolded, hyperphosphorylated tau protein, are a pathological hallmark of several neurodegenerations, including Alzheimer's disease. Tau pathology spreads between neurons and propagates misfolding in a prion-like manner throughout connected neuronal circuits. Tauopathy is accompanied by significant neur...
Article
Objectives The use of primary human neural tissue for research provides an invaluable insight into human neural function that cannot be achieved in any other way. Despite this it is successfully collected and used in only a small minority of units. We have established a collaboration between Neurosurgical Unit and the University that allows us to s...
Article
Full-text available
The synaptic changes underlying the onset of cognitive impairment in Alzheimer's disease (AD) are poorly understood. In contrast to the well documented inhibition of long-term potentiation (LTP) in CA3-CA1 synapses by acute Aβ application in adult neurons from rodents, young amyloid precursor protein (APP) transgenic mouse models often, surprisingl...
Article
The use of primary human neural tissue for research provides an invaluable insight into human neural function that cannot be achieved in any other way. Despite this it is successfully collected and used in only a small minority of units. We have established a collaboration between the Wessex Neurological Centre and the University of Southampton tha...
Preprint
Full-text available
In Alzheimer's disease, misfolded tau protein propagates through the brain in a prion-like manner along connected circuits. Tauopathy correlates with significant neuronal death, but the links between tau aggregation, propagation, neuronal dysfunction and death remain poorly understood, and the direct functional consequences for the neuron containin...
Article
Full-text available
Microtubule associated protein tau (MAPT) is involved in the pathogenesis of Alzheimer's disease and many forms of frontotemporal dementia (FTD). We recently reported that Aβ-mediated inhibition of hippocampal long-term potentiation (LTP) in mice requires tau. Here, we asked whether expression of human MAPT can restore Aβ-mediated inhibition on a m...
Article
Full-text available
Microtubule associated protein tau (MAPT) is involved in the pathogenesis of Alzheimer’s disease and many forms of frontotemporal dementia (FTD). We recently reported that Aβ-mediated inhibition of hippocampal long-term potentiation (LTP) in mice requires tau. Here, we asked whether expression of human $MAPT$ can restore Aβ-mediated inhibition on a...
Article
Full-text available
Most cortical neurons fire regularly when excited by a constant stimulus. In contrast, irregular-spiking (IS) interneurons are remarkable for the intrinsic variability of their spike timing, which can synchronize amongst IS cells via specific gap junctions. Here, we have studied the biophysical mechanisms of this irregular spiking in mice, and how...
Article
Introduction: Although many disease models exist for neurodegenerative disease, the translation of basic research findings to clinic is very limited. Studies using freshly resected human brain tissue, commonly discarded from neurosurgical procedures, should complement on-going work using stem cell-derived human neurons and glia thus increasing the...
Article
The proliferation and activation of microglial cells is a hallmark of several neurodegenerative conditions. This mechanism is regulated by the activation of the colony-stimulating factor 1 receptor (CSF1R), thus providing a target that may prevent the progression of conditions such as Alzheimer's disease. However, the study of microglial proliferat...
Chapter
Full-text available
Microfabrication protocols are described for two compartmentalized neuron culture platforms which extend beyond the capabilities of conventional systems. The fi rst involves a differential fl ow microfl uidic circuit for arraying single neurons, along with protocols for in chip biomaterial patterning and the selective treatment of somata or outgrow...
Article
Full-text available
The study of neurogenesis during chronic neurodegeneration is crucial in order to understand the intrinsic repair mechanisms of the brain, and key to designing therapeutic strategies. In this study, using an experimental model of progressive chronic neurodegeneration, murine prion disease, we define the temporal dynamics of the generation, maturati...
Article
Full-text available
The study of neurogenesis during chronic neurodegeneration is crucial in order to understand the intrinsic repair mechanisms of the brain, and key to designing therapeutic strategies. In this study, using an experimental model of progressive chronic neurodegeneration, murine prion disease, we define the temporal dynamics of the generation, maturati...
Article
Full-text available
Amyloid β (Aβ) and tau protein are both implicated in memory impairment, mild cognitive impairment (MCI), and early Alzheimer's disease (AD), but whether and how they interact is unknown. Consequently, we asked whether tau protein is required for the robust phenomenon of Aβ-induced impairment of hippocampal long-term potentiation (LTP), a widely ac...
Article
Full-text available
GABA(A) receptors that contain the alpha5 subunit (alpha5GABA(A)Rs) are highly expressed in the hippocampus, and have been implicated in learning and memory processes. They generate a tonic form of inhibition that regulates neuronal excitability. Recently it was shown that alpha5GABA(A)Rs also contribute to slow phasic inhibition of CA1 pyramidal n...
Article
Full-text available
Chronic pain hypersensitivity depends on N-methyl-D-aspartate receptors (NMDARs). However, clinical use of NMDAR blockers is limited by side effects resulting from suppression of the physiological functions of these receptors. Here we report a means to suppress pain hypersensitivity without blocking NMDARs, but rather by inhibiting the binding of a...
Article
Full-text available
Phagosomes employ lytic enzymes, cationic peptides, and reactive oxygen intermediates to eliminate invading microorganisms. The effectiveness of these microbicidal mechanisms is potentiated by the acidic pH created by H⁺-pumping vacuolar-type ATPases (V-ATPases) on the phagosomal membrane. The degree of phagosomal acidification varies greatly among...
Article
Local GABA (gamma-aminobutyric acid) circuits contribute to sensory experience-dependent refinement of neuronal connections in the developing nervous system, but whether GABAergic synapses themselves can be rapidly modified by sensory stimuli is largely unknown. Here we report that repetitive light stimuli or theta burst stimulation (TBS) of the op...
Article
Full-text available
The NMDA receptor (NMDAR) produces a long-lasting component of the glutamatergic EPSC in mammalian central neurons. The current through NMDARs is voltage dependent as a result of block by extracellular magnesium, which has recently been shown to give rise to a complex time dependence, with fast and slow components of responses to changes in membran...
Article
Full-text available
Interactions among chemical and electrical synapses regulate the patterns of electrical activity of vertebrate and invertebrate neurons. In this investigation we studied how electrical coupling influences the integration of excitatory postsynaptic potentials (EPSPs). Pairs of Retzius neurons of the leech are coupled by a nonrectifying electrical sy...
Article
Full-text available
The timing of voltage-dependent removal of Mg(2+) block of N-methyl-d-aspartate receptors (NMDARs) is potentially critical for determining their nonlinear contribution to excitability. Here, we measure the kinetics of NMDAR unblock in nucleated patch and whole cell recordings of rat cortical pyramidal neurons during depolarizing voltage steps. At r...
Article
Full-text available
We studied the spread of excitatory postsynaptic potentials (EPSPs) through electrical synapses in Retzius neurones of the leech Haementeria officinalis. The pair of Retzius neurones in each ganglion is coupled by a non-rectifying electrical synapse. Both neurones displayed synchronous EPSPs of varying amplitudes and rise times. The kinetics of syn...

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