A5046973306- Neuroscience and Neuropharmacology Research
- Genetic Neurodegenerative Diseases
- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurological disorders and treatments
- Mitochondrial Function and Pathology
- Neuroscience and Neural Engineering
- Inflammation biomarkers and pathways
- Photoreceptor and optogenetics research
- Ion channel regulation and function
- Bioinformatics and Genomic Networks
- Memory and Neural Mechanisms
- Parkinson's Disease Mechanisms and Treatments
- Nicotinic Acetylcholine Receptors Study
- Neural dynamics and brain function
- 3D Printing in Biomedical Research
- Conducting polymers and applications
- Nuclear Receptors and Signaling
- Neurotransmitter Receptor Influence on Behavior
- Smoking Behavior and Cessation
- Neurological Disease Mechanisms and Treatments
- Adipose Tissue and Metabolism
- Connexins and lens biology
- Down syndrome and intellectual disability research
- Immune cells in cancer
University College London
2016-2025
Transnational Press London
2015-2021
University of California, Los Angeles
2006-2019
GlaxoSmithKline (United Kingdom)
2018
The Open University
2004-2016
Huntington's Disease Association
2011-2016
Intel (United States)
2011
We provide microarray data comparing genome-wide differential expression and pathology throughout life in four lines of "amyloid" transgenic mice (mutant human APP, PSEN1, or APP/PSEN1) "TAU" MAPT gene). Microarray were validated by qPCR comparison to studies, including association study (GWAS) hits. Immune gene correlated tightly with plaques whereas synaptic genes negatively neurofibrillary tangles. Network analysis immune modules revealed six hub hippocampus amyloid mice, common cortex....
Previously, we identified progressive alterations in spontaneous EPSCs and IPSCs the striatum of R6/2 mouse model Huntington's disease (HD). Medium-sized spiny neurons from these mice displayed a lower frequency EPSCs, population cells exhibited an increased beginning at ∼40 d, time point when overt behavioral phenotype begins. The cortex provides major excitatory drive to is affected during progression. We examined somatosensory cortical pyramidal layers II/III slices three different models...
Huntington disease is a genetic neurodegenerative disorder that produces motor, neuropsychiatric, and cognitive deficits caused by an abnormal expansion of the CAG tract in huntingtin (htt) gene. In humans, mutated htt induces preferential loss medium spiny neurons striatum and, to lesser extent, cortical as progresses. The mechanisms causing these degenerative changes remain unclear, but they may involve synaptic dysregulation. We examined activity corticostriatal pathway using combination...
Neurofibromatosis type I (NF1) is one of the most common single-gene causes learning disabilities. Here, we use behavioral working memory probes and electrophysiological studies in a mouse model NF1 ( Nf1 heterozygous null mutants; +/− ) to demonstrate that i Neurofibromin regulates prefrontal striatal inhibitory networks, specifically activity-dependent GABA release ii required for performance, with inhibition-dependent deficits seen mice. We find increased inhibition medial cortex (mPFC)...
Abstract Genome-wide association studies have reported that, amongst other microglial genes, variants in TREM2 can profoundly increase the incidence of developing Alzheimer’s disease (AD). We investigated role primary cultures from wild type mice by using siRNA to decrease Trem2 expression, and parallel knock-in heterozygous or homozygous for R47H AD risk variant. The prevailing phenotype was decreased expression levels microglia, which resulted density microglia hippocampus. Overall, with...
Abstract Genome-wide association studies of late-onset Alzheimer’s disease risk have previously identified genes primarily expressed in microglia that form a transcriptional network. Using transgenic mouse models amyloid deposition, we showed many the orthologues these are co-expressed and associated with pathology. In this new study, generate an improved RNA-seq-derived network is amyloid-responsive statistically compare gene-level variation previous human genome-wide to predict at least...
Huntington's disease (HD) is a fatal neurodegenerative disorder characterized by progressive motor, psychiatric and cognitive decline. Marked neuronal loss occurs in the cortex striatum. HD inherited an autosomal dominant fashion caused trinucleotide repeat expansion (CAG) gene encoding protein huntingtin. Predictive genetic testing has revealed early deficits asymptomatic carriers at time when there little evidence for cell death, suggesting that impaired cognition results from cellular or...
Predictive genetic testing for Huntington's disease (HD) has revealed early cognitive deficits in asymptomatic gene carriers, such as altered working memory, executive function and impaired recognition memory. The perirhinal cortex processes aspects of memory the underlying mechanism is believed to be long-term depression (LTD) excitatory neurotransmission, converse potentiation (LTP). We have used R6/1 mouse model HD assess synaptic plasticity cortex. report here a progressive derailment...
Striatal medium-sized spiny neurons (MSSNs) receive glutamatergic inputs modulated presynaptically and postsynaptically by dopamine. Mice expressing the gene for enhanced green fluorescent protein as a reporter to identify MSSNs containing D1 or D2 receptor subtypes were used examine dopamine modulation of spontaneous excitatory postsynaptic currents (sEPSCs) in slices N-methyl-d-aspartate (NMDA) alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) acutely isolated cells. The...
Detecting and treating Alzheimer’s disease, before cognitive deficits occur, has become the health challenge of our time. The earliest known event in disease is rising amyloid-β. Previous studies have suggested that effects on synaptic transmission may precede plaque deposition. Here we report how relative levels different soluble amyloid-β peptides hippocampus, preceding deposition, relate to genomic changes. Immunoprecipitation-mass spectrometry was used measure early rise a mouse model...
Abstract Background Microglia are active modulators of Alzheimer’s disease but their role in relation to amyloid plaques and synaptic changes due rising beta is unclear. We add novel findings concerning these relationships investigate which our previously reported results from transgenic mice can be validated knock-in mice, overexpression other artefacts technology avoided. Methods App NL-F NL-G-F expressing humanised with mutations that cause familial were compared wild type throughout...
Since the identification of gene responsible for HD (Huntington's disease), many genetic mouse models have been generated. Each employs a unique approach delivery mutated and has different CAG repeat length background strain. The resultant diversity in context phenotypes these led to extensive debate regarding relevance each model human disorder. Here, we compare contrast striatal synaptic two HD, namely YAC128 mouse, which carries full-length huntingtin on yeast artificial chromosome,...
The R6/2 mouse is the most frequently used model for experimental and preclinical drug trials in Huntington's disease (HD). When was first developed, it carried exon 1 of huntingtin gene with ∼150 cytosine-adenine-guanine (CAG) repeats. presented a rapid aggressive phenotype that shared many features human condition particularly similar to juvenile HD. However, instability CAG repeat length due different breeding practices has led both decreases increases average lengths among colonies....
<title>Abstract</title> Understanding how amyloid beta (Aβ) plaques form and progress to neurotoxicity in Alzheimer’s disease remains a significant challenge. This study aims elucidate the processes involved Aβ plaque formation maturation using knock-in mouse model (AppNL- F/NL-F). By employing mass spectrometry imaging stable isotope labeling, we timestamped from their initial deposition, enabling spatial tracking of aging. Correlating single-plaque transcriptomics with time since seeding,...
ORIGINAL RESEARCH article Front. Syst. Neurosci., 11 May 2011 | https://doi.org/10.3389/fnsys.2011.00028
<i>Background:</i> The introduction of gene testing for Huntington’s disease (HD) has enabled the neuropsychiatric and cognitive profiling human carriers prior to onset overt motor symptoms. Such studies reveal an early decline in working memory executive function, altered EEG a loss striatal dopamine receptors. Working is processed prefrontal cortex modulated by extrinsic dopaminergic inputs. <i>Objective:</i> We sought study excitatory synaptic function plasticity...
Neuronal pentraxin 1 (NPTX1) has been implicated in Alzheimer's disease, being present and around dystrophic neurons plaques, affecting glutamatergic transmission postsynaptically mediating effects of amyloidβ. Here, we confirm the presence NPTX1 plaques postmortem disease brain report that acutely applied human increases paired-pulse ratio at mouse CA3-CA1 hippocampal synapses, indicating a decrease glutamate release. In contrast, chronic exposure to NPTX1, NPTX2, or NPTX receptor decreases...
Abstract 3D objects with integrated electronics are produced using an additive manufacturing approach relying on multiphoton fabrication (direct laser writing, (DLW)). Conducting polymer‐based structures (with micrometer‐millimeter scale features) printed within exemplar matrices, including elastomer (polydimethylsiloxane, (PDMS)) have been widely investigated for biomedical applications. The fidelity of the printing process in PDMS is assessed by optical coherence tomography, and conducting...
In the R6/2 mouse model of Huntington's disease (HD) we examined effects a number behavioral and pharmacological manipulations aimed at rescuing progressive loss synaptic communication between cerebral cortex striatum. Two cohorts transgenic mice with ~110 210 CAG repeats were utilized. Exercise prevented reduction in striatal medium-sized spiny neuron membrane capacitance but did not reestablish communication. Activation adenosine A2A type receptors renormalized postsynaptic activity to...