A5047839634- MicroRNA in disease regulation
- Neuroscience and Neuropharmacology Research
- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- Epilepsy research and treatment
- Antenna Design and Analysis
- Electromagnetic Compatibility and Measurements
- Antenna Design and Optimization
- Neural dynamics and brain function
- Electromagnetic Scattering and Analysis
- Cancer-related molecular mechanisms research
- Advanced Antenna and Metasurface Technologies
- RNA regulation and disease
- Microwave and Dielectric Measurement Techniques
- Pharmacological Effects and Toxicity Studies
- RNA Research and Splicing
- Microwave Engineering and Waveguides
- Neuroscience and Neural Engineering
- Adenosine and Purinergic Signaling
- Memory and Neural Mechanisms
- Circular RNAs in diseases
- Machine Learning in Bioinformatics
- EEG and Brain-Computer Interfaces
- Ultrasound Imaging and Elastography
- Functional Brain Connectivity Studies
Royal College of Surgeons in Ireland
2019-2024
University College London
2016-2024
Science Foundation Ireland
2020-2023
University of Manchester
2023
Manchester Academic Health Science Centre
2023
University of Liverpool
2021-2023
University of Medicine and Health Sciences
2022
Molecular Medicine Ireland
2022
Czech Academy of Sciences, Institute of Physiology
2019
Cardiff University
2017
Current anti-epileptic drugs (AEDs) act on a limited set of neuronal targets, are ineffective in third patients with epilepsy, and do not show disease-modifying properties. MicroRNAs small noncoding RNAs that regulate levels proteins by post-transcriptional control mRNA stability translation. MicroRNA-134 is involved controlling microstructure brain excitability previous studies showed intracerebroventricular injections locked nucleic acid (LNA), cholesterol-tagged antagomirs targeting...
Temporal lobe epilepsy is the most common drug-resistant form of in adults. The reorganization neural networks and gene expression landscape underlying pathophysiologic network behavior brain structures such as hippocampus has been suggested to be controlled, part, by microRNAs. To systematically assess their significance, we sequenced Argonaute-loaded microRNAs define functionally engaged three different animal models two species at six time points between initial precipitating insult...
There remains an urgent need for new therapies treatment-resistant epilepsy. Sodium channel blockers are effective seizure control in common forms of epilepsy, but loss sodium function underlies some genetic Approaches that provide bidirectional expression needed. MicroRNAs (miRNA) small noncoding RNAs which negatively regulate gene expression. Here we show genome-wide miRNA screening hippocampal tissue from a rat epilepsy model, mice treated with the antiseizure medicine cannabidiol, and...
The diagnosis of epilepsy is complex and challenging would benefit from the availability molecular biomarkers, ideally measurable in a biofluid such as blood. Experimental human are associated with altered brain blood levels various microRNAs (miRNAs). Evidence lacking, however, to whether any circulating pool miRNAs originates brain. To explore link between pathophysiology epilepsy, we first sequenced argonaute 2 (Ago2)-bound plasma samples collected mice subject status epilepticus induced...
Carvacrol is a naturally occurring monoterpenic phenol that has been suggested to have an action at transient receptor potential cation subfamily M7 (TRPM7) channels, γ-aminobutyric acid (GABAA receptors, and sodium shown be antiinflammatory. neuroprotective in models of cerebral ischemia vivo vitro, probably through its TRPM7 channels. We therefore aimed determine the effect carvacrol on status epilepticus (SE), chronic epilepsy, cell death, post-SE cognitive decline.We performed long-term,...
Mesial temporal lobe epilepsy (mTLE) is a chronic neurological disease characterized by recurrent seizures. The antiepileptic drugs currently available to treat mTLE are ineffective in one-third of patients and lack disease-modifying effects. miRNAs, class small noncoding RNAs which control gene expression at the post-transcriptional level, play key role pathogenesis other epilepsies. Although manipulation miRNAs acute stages has been reported reduce subsequent spontaneous seizures, it...
Background and Purpose Refractory status epilepticus is a clinical emergency associated with high mortality morbidity. Increasing evidence suggests neuroinflammation contributes to the development of drug‐refractoriness during epilepticus. Here, we have determined contribution ATP‐gated P2X7 receptor, previously linked inflammation increased hyperexcitability, drug‐refractory its therapeutic potential. Experimental Approach Status was induced via unilateral microinjection kainic acid into...
Abstract Objective. Electroencephalography (EEG) is a key tool for non-invasive recording of brain activity and the diagnosis epilepsy. EEG monitoring also widely employed in rodent models to track epilepsy development evaluate experimental therapies interventions. Whereas automated seizure detection algorithms have been developed clinical EEG, preclinical versions face challenges inter-model differences lack standardization, leaving researchers relying on time-consuming visual annotation...
Angelman syndrome (AS) is a severe neurodevelopmental disorder featuring ataxia, cognitive impairment, and drug-resistant epilepsy. AS caused by mutations or deletion of the maternal copy paternally imprinted UBE3A gene, with current precision therapy approaches focusing on re-expression UBE3A. Certain phenotypes, however, are difficult to rescue beyond early development. Notably, cluster microRNA binding sites was reported in untranslated Ube3a1 transcript, including for miR-134, suggesting...
Abstract Epileptogenesis is the process by which a normal brain becomes hyperexcitable and capable of generating spontaneous recurrent seizures. The extensive dysregulation gene expression associated with epileptogenesis shaped, in part, microRNAs (miRNAs) – short, non-coding RNAs that negatively regulate protein levels. Functional miRNA-mediated regulation can, however, be difficult to elucidate due complexity miRNA-mRNA interactions. Here, we integrated miRNA mRNA profiles sampled over...
Abstract Background Breast cancer brain metastasis is a rising occurrence, necessitating better understanding of the mechanisms involved for effective management. metastases diverge notably from primary tumor, with gains in kinase and concomitant losses steroid signaling observed. In this study, we explored role receptor RET promoting breast provide rationale targeting receptor. Methods expression was characterized cohort patients metastatic tumors. functionality assessed using...
Traditionally, visually-guided patch clamp in brain slices using submerged recording conditions has been required to characterise the activity of individual neurons. However, due limited oxygen availability, truncate fast network oscillations including epileptiform activity. Thus it is technically challenging study contribution identified neurons The membrane chamber a submerged-style chamber, modified enhance supply slice, which we use demonstrate ability record single-cell during vitro...
Abstract MicroRNAs are short non-coding RNAs that negatively regulate protein levels and perform important roles in establishing maintaining neuronal network function. Previous studies adult rodents have detected upregulation of microRNA-134 after prolonged seizures (status epilepticus) demonstrated silencing using antisense oligonucleotides, termed antagomirs, has potent long-lasting seizure-suppressive effects. Here we investigated whether targeting can reduce or delay acute the immature...
Dravet syndrome (DS) is a catastrophic form of pediatric epilepsy mainly caused by noninherited mutations in the SCN1A gene. DS patients suffer severe and life-threatening focal generalized seizures which are often refractory to available anti-seizure medication. Antisense oligonucleotides (ASOs) based approaches may offer treatment opportunities DS. MicroRNAs short noncoding RNAs that play key role brain structure function post-transcriptionally regulating gene expression, including ion...
Summary Objective Inhibition of micro RNA ‐134 by an oligonucleotide antagomir (ant‐134) has been shown to produce powerful antiseizure effects in multiple models epilepsy. However, successfully translate the treatment clinic, it is important assess what potential adverse may have on naive brain tissue. Methods To investigate this, adult male Sprague‐Dawley rats were treated with either ant‐134 or a scrambled control sequence. Animals later assessed for spatial navigation, before ex vivo...
MicroRNAs are non-coding RNAs, approximately 22 nt in length, which serve to negatively regulate gene expression through binding complementary sequences the 3' untranslated region (3'UTR) of target mRNA. The microRNA-target interaction does not require perfect complementarity, meaning that an individual microRNA often has a pool hundreds targets. Equally, one 3'UTR can contain sites for many different microRNAs. This gives rise complex web molecular interactions. An emerging concept is...
Although relatively new, the principle of measuring radiation pattern an antenna using time domain rather than frequency is well known and relies on gating out unwanted reflections. Time measurements horn spiral antennas illustrate need for error criteria in this paper nature error, its relationship to anti-interference enclosure size response, are investigated by both analytical computer simulation methods. The results show that a lower can be expected require larger given that, small...
A major challenge in experimental epilepsy research is to reconcile the effects of anti-epileptic drugs (AEDs) on individual neurons with their network-level actions. Highlighting this difficulty, it unclear why carbamazepine (CBZ), a frontline AED known molecular mechanism, has been reported increase epileptiform activity several clinical and studies. We confirmed an vitro mouse model (in both sexes) that frequency interictal bursts increased after CBZ perfusion. To address underlying...
Intellectual disability affects 2–3% of the population; mutations X-chromosome are a major cause moderate to severe cases. The link between molecular consequences mutation and impaired cognitive function remains unclear. Loss oligophrenin-1 (OPHN1) disrupt Rho-GTPase signalling. Here we demonstrate abnormal neurotransmission at CA3 synapses in hippocampal slices from Ophn1-/y mice, resulting substantial decrease readily releasable pool vesicles. As result, synaptic transmission fails high...
Advancement of understanding the etiology and treatment epilepsy has largely depended on use acute chronic animal models. An alternative approach, which is being increasingly used by a select number laboratories worldwide, to perform functional mechanistic studies in brain slices living human tissue resected during surgery for drug resistant epilepsies. Pharmacoresistant major clinical problem with significant proportion patients not receiving any symptomatic benefit from available...
Antisense inhibition of microRNAs is an emerging preclinical approach to pharmacoresistant epilepsy. A leading candidate "antimiR" targeting microRNA-134 (ant-134), but testing date has used rodent models. Here, we develop antimiR platform in human brain tissue sections. Brain specimens were obtained from patients undergoing resective surgery treat Neocortical submerged modified artificial cerebrospinal fluid (ACSF) and dissected for clinical neuropathological examination, unused material...