A5053026356- Neuroscience and Neuropharmacology Research
- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Cellular transport and secretion
- Memory and Neural Mechanisms
- Stress Responses and Cortisol
- Neurological Disease Mechanisms and Treatments
- Neurogenesis and neuroplasticity mechanisms
- Receptor Mechanisms and Signaling
- Retinal Development and Disorders
- Nicotinic Acetylcholine Receptors Study
- Epigenetics and DNA Methylation
- Lipid Membrane Structure and Behavior
- Mitochondrial Function and Pathology
- Genetics and Neurodevelopmental Disorders
- Neuroscience and Neural Engineering
- Autism Spectrum Disorder Research
- Photoreceptor and optogenetics research
- Calcium signaling and nucleotide metabolism
- Adenosine and Purinergic Signaling
- Tryptophan and brain disorders
- Neuroendocrine regulation and behavior
University of Bath
2023
University of Bristol
2011-2021
Wellcome Trust
2015-2016
The microtubule-associated protein tau is a principal component of neurofibrillary tangles, and has been identified as key molecule in Alzheimer's disease other tauopathies. However, it unknown how that primarily located axons involved believed to have synaptic origin. To investigate possible function tau, we studied plasticity the hippocampus found selective deficit long-term depression (LTD) knockout mice vivo vitro, an effect was replicated by RNAi knockdown vitro. We induction LTD...
Tau is required for the induction of long-term depression (LTD) synaptic transmission in hippocampus. Here we probe role tau LTD, finding that an AMPA receptor internalization mechanism impaired KO mice, and LTD causes specific phosphorylation at serine 396 404 residues tau. Surprisingly, find 396, specifically, critical but has no LTP. Finally, show mice exhibit deficits spatial reversal learning. These findings underscore physiological synapse identify a behavioral correlate its LTD.
Abstract The acute neurotoxicity of oligomeric forms amyloid-β 1-42 (Aβ) is implicated in the pathogenesis Alzheimer’s disease (AD). However, how these oligomers might first impair neuronal function at onset pathology poorly understood. Here we have examined underlying toxic effects caused by an increase levels intracellular Aβ, event that could be important during early stages disease. We show oligomerised Aβ induces a rapid enhancement AMPA receptor-mediated synaptic transmission (EPSC A )...
The neuroendocrine response to episodes of acute stress is crucial for survival whereas the prolonged chronic can be detrimental. Learning and memory are particularly susceptible with cognitive deficits being well characterized consequences stress. Although there good evidence that enhance performance, mechanism(s) this unclear. We find hippocampal slices, either prepared from rats following 30 min restraint or directly exposed glucocorticoids, exhibit an N-methyl-d-aspartic acid...
The G-protein coupled receptor family of glutamate receptors, termed metabotropic receptors (mGluRs), are implicated in numerous cellular mechanisms ranging from neural development to the processing cognitive, sensory, and motor information. Over last decade, multiple mGluR-related signal cascades have been identified at excitatory synapses, indicating their potential roles various forms synaptic function dysfunction. This review highlights recent studies investigating mGluR5, a subtype...
Mounting evidence suggests that the etiology of autism spectrum disorders (ASDs) is profoundly influenced by exposure to environmental factors, although precise molecular and cellular links remain ill-defined. In this study, we examined how valproic acid (VPA) during pregnancy associated with an increased incidence ASD. A mouse model was established injecting VPA at embryonic day 13, its behavioral phenotypes including impaired social interaction, repetitive behaviors decreased nociception...
Despite being a highly enriched synaptic vesicle (SV) protein and candidate gene for autism, the physiological function of SCAMP5 remains mostly enigmatic. Here, using optical imaging electrophysiological experiments, we demonstrate that plays critical role in release site clearance at active zone. Truncation analysis revealed 2/3 loop domain directly interacts with adaptor 2, this interaction is its clearance. Knockdown (KD) exhibited pronounced depression accompanied by slower recovery SV...
Hyperphosphorylation of the microtubule associated protein tau (tau) is inextricably linked to several neurodegenerative diseases, collectively termed tauopathies, in which synapse dysfunction occurs through largely unidentified mechanisms. Our research aimed uncover molecular mechanisms by phosphorylation (pTau) affects function. Using combined and electrophysiological analysis with vitro genetic knock-in mutant human male rat CA1 hippocampal neurons, we show an interplay between kinase C...
Abstract Cyclin Y (CCNY) is a member of the cyclin protein family, known to regulate cell division in proliferating cells. Interestingly, CCNY expressed neurons that do not undergo division. Here, we report negatively regulates long-term potentiation (LTP) synaptic strength through inhibition AMPA receptor trafficking. enriched postsynaptic fractions from rat forebrain and localized adjacent sites dendritic spines hippocampal neurons. Using live-cell imaging pH-sensitive receptor, found...
Neuronal calcium sensors (NCS) readily bind and undergo conformational changes enabling them to interact regulate specific target molecules. These interactions lead dynamic alterations in protein trafficking that significantly impact upon synaptic function. Emerging evidence suggests NCS Ca(2+) mobilization modulate glutamate receptor trafficking, subsequently determining the expression of different forms plasticity. In this review, we aim discuss functional relevance their emerging role...
It is well documented that reactive oxygen species (ROS) affects neurodegeneration in the brain. Several studies also implicate ROS regulation of synapse function and learning memory processes, although precise source generation within these contexts remains to be further explored. Here we show postsynaptic superoxide through PKCζ-activated NADPH oxidase 2 (NOX2) critical for long-term depression (LTD) synaptic transmission CA1-Shaffer collateral rat hippocampus. Specifically, PKCζ-dependent...
Microglia are crucial players in the pathogenesis of late-onset Alzheimer's disease (AD), with evidence for both deleterious and beneficial effects. Identifying interventions to modulate microglial responsiveness, promote amyloid β (Aβ) clearance, disrupt plaque formation, or dampen excessive inflammation has therapeutic potential. Bioavailable flavonoids, such as flavan 3-ols, interest due their antioxidant, metal chelating, signalling, anti-inflammatory Primary microglia were treated a...
Abstract Microglia are crucial players in the pathogenesis of late onset Alzheimer’s Disease (AD), with evidence for both deleterious and beneficial effects. Identifying interventions to modulate microglial responsiveness, promote Amyloid β (Aβ) clearance, disrupt plaque formation or dampen excessive inflammation has therapeutic potential. Bioavailable flavonoids such as flavan 3-ols interest due their antioxidant, metal chelating, signalling anti-inflammatory Primary microglia were treated...