Saak Ovsepian

Saak Ovsepian
University of Greenwich · School of Science

Professor in Biosciences
Biosciences, Neurobiology, Molecular Imaging

About

140
Publications
33,011
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2,539
Citations
Additional affiliations
February 2008 - present
International Center for Neurotheraeutics Dublin
Position
  • Faculty Member

Publications

Publications (140)
Article
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Dendritic exocytosis underpins a broad range of integrative and homeostatic synaptic functions. Emerging data highlight the essential role of SNAREs in trafficking and fusion of secretory organelles with release of peptides and neurotransmitters from dendrites. This Perspective analyzes recent evidence inferring axo-dendritic polarization of vesicu...
Article
Alzheimer disease (AD) is characterized by the accumulation of amyloid plaques, which are predominantly composed of amyloid-β peptide. Two principal physiological pathways either prevent or promote amyloid-β generation from its precursor, β-amyloid precursor protein (APP), in a competitive manner. Although APP processing has been studied in great d...
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Little is known how synaptically released endogenous ACh affects hippocampal synaptic plasticity in vivo. Here, we examined the role of cholinergic drive in the regulation of the induction of long-term potentiation (LTP) at basal dendrites in the CA1 area of the anaesthetized rat hippocampus. The non-subtype selective muscarinic acetylcholine recep...
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Celiac disease (CeD) manifests with autoimmune intestinal inflammation from gluten and genetic predisposition linked to human leukocyte antigen class-II (HLA-II) gene variants. Antigen-presenting cells facilitate gluten exposition through the interaction of their surface major histocompatibility complex (MHC) with the T cell receptor (TCR) on T lym...
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Neurodegenerative diseases (NDDs) are associated with the accumulation of a range of misfolded proteins across the central nervous system and related autoimmune responses, including the generation of antibodies and the activation of immune cells. Both innate and adaptive immunity become mobilized, leading to cellular and humoral effects. The role o...
Article
The cerebellum hosts more than half of all neurons of the human brain, with their organized activity playing a key role in coordinating motor functions. Cerebellar activity has also been implicated in the control of speech, communication, and social behavior, which are compromised in autism spectrum disorders (ASD). Despite major research advances,...
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Ever since its first use in surgery, general anesthesia has been regarded as a medical miracle enabling countless life-saving diagnostic and therapeutic interventions without pain sensation and traumatic memories. Despite several decades of research, there is a lack of understanding of how general anesthetics induce a reversible coma-like state. Em...
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Notwithstanding major advances in psychotherapeutics, their efficacy and specificity remain limited. The slow onset of beneficial outcomes and numerous adverse effects of widely used medications remain of chief concern, warranting in-depth studies. The majority of frontline therapies are thought to enhance the endogenous monoaminergic drive, to ini...
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Glioblastoma multiforme (GBM) is a primary brain cancer of poor prognosis, with existing treatments remaining essentially palliative. Current GBM therapy fails due to rapid reappearance of the heterogeneous neoplasm, with models suggesting that the recurrent growth is from treatment-resistant glioblastoma stem-like cells (GSCs). Whether GSCs depend...
Article
Although produced largely in the periphery, gonadal steroids play a key role in regulating the development and functions of the central nervous system and have been implicated in several chronic neuropsychiatric disorders, with schizophrenia and Alzheimer’s disease (AD) most prominent. Despite major differences in pathobiology and clinical manifest...
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Neuroblastoma cell line SH-SY5Y, due to its capacity to differentiate into neurons, easy handling, and low cost, is a common experimental model to study molecular events leading to Alzheimer’s disease (AD). However, it is prevalently used in its undifferentiated state, which does not resemble cells affected by the disease. Here, we show that the ex...
Article
The disproportionate evolutionary expansion of human cerebral cortex with reinforcement of cholinergic innervations warranted the rise in functional and metabolic load of conserved basal forebrain (BF) cholinergic system. Given that acetylcholine (ACh) regulates the properties of microtubule-associated protein (MAP) tau and promotes non-amyloidogen...
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The successful development of innovative neurotherapies to restore synaptic functions and neural communication affected by disorders (e.g. chronic pain, neurodegenerative and neuropsychiatric conditions) requires an in-depth understanding of cellular and molecular mechanisms involved. Dr James Oliver Dolly, Science Foundation Ireland (SFI) Professo...
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The reinstatement and revision of abandoned therapeutic ventures of the past has been an integral part of medical research and advancement. In psychiatry, much interest was generated recently by emerging data on the use of faecal supplements for restoring the neurochemical balance in the brain, and on the ingestion of placenta to stabilize neural c...
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Methamphetamine is a potent and highly addictive psychostimulant, and one of the most widely used illicit drugs. Over recent years, its global usage and seizure have been on a rapid rise, with growing detrimental effects on mental and physical health, and devastating psychosocial impact pressing for intervention. Among the unwanted effects of metha...
Article
Tuberous sclerosis complex (TSC) is a dominant autosomal genetic disorder caused by loss-of-function mutations in TSC1 and TSC2, which lead to constitutive activation of the mammalian target of rapamycin C1 (mTORC1) with its decoupling from regulatory inputs. Because mTORC1 integrates an array of molecular signals controlling protein synthesis and...
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An enigmatic localized pneumonia escalated into a worldwide COVID-19 pandemic from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This review aims to consolidate the extensive biological minutiae of SARS-CoV-2 which requires decipherment. Having one of the largest RNA viral genomes, the single strand contains the genes ORF1ab, S, E,...
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Schizophrenia is a chronic neuropsychiatric brain disorder that has devastating personal impact and rising healthcare costs. Dysregulation of glutamatergic neurotransmission has been implicated in the pathobiology of the disease, attributed largely to the hypofunction of the N-methyl-D-aspartate (NMDA) receptor. Currently, there is a major gap in t...
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The dazzling complexity of the brain not only challenges the human imagination and intellectual brilliance but also exposes faults and limitations of the most advanced tools and research methods. With over 100 billion neurons, each of them forming many thousands of contacts, the human brain is arguably the most sophisticated natural invention. It i...
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Epilepsy is one of the most prevalent and devastating neurological disorders characterized by episodes of unusual sensations, loss of awareness, and reoccurring seizures. The frequency and intensity of epileptic fits can vary to a great degree, with almost a third of all cases resistant to available therapies. At present, there is a major unmet nee...
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Full-text available
The successful development of innovative neurotherapies to restore synaptic functions and neural communication affected by disease (e.g. chronic pain, neurodegenerative and neuropsychiatric diseases) requires in-depth understanding of cellular and molecular mechanisms involved. Dr. James Oliver Dolly, Science Foundation Ireland Professor of Neuroth...
Article
Epilepsy is one of the commonest neurological diseases, though convulsive seizures cannot be completely cured in 30% of patients, such that there is a need to develop new pharmacological approaches to its treatment. In some pathological states, including drug-resistant forms of epilepsy, the mechanisms removing glutamate from the synaptic cleft may...
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https://authors.elsevier.com/a/1buvWcQbIzDxE Accessible for 50 days.
Article
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Although the neurocognitive deficit is the best-recognized indicator of Alzheimer’s disease (AD), psychotic and other noncognitive symptoms are the prime cause of institutionalization. BACE1 is the rate-limiting enzyme in the production of Aβ of AD, and one of the promising therapeutic targets in countering the cognitive decline and amyloid patholo...
Chapter
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Synaptic transmission is a fundamental neurobiological process by which neurons interact with each other and non-neuronal cells. The process involves release of active substances from the presynaptic neuron onto receptive elements of postsynaptic cells, inducing waves of spreading electrochemical response. While much has been learned about the cell...
Article
Throughout development, neuronal progenitors undergo complex transformation into polarized nerve cells, warranting the directional flow of information in a neural grid. The majority of neuronal polarization studies have been carried out on rodent-derived precursor cells, programmed to develop into neurons. Unlike these rodent neuronal cells, SH-SY5...
Article
Tuberous sclerosis complex (TSC) is a genetic disorder characterized by frequent noncancerous neoplasia in the brain, which can induce a range of severe neuropsychiatric symptoms in humans, resulting from out of control tissue growth. The causative spontaneous loss-of-function mutations have been also identified in rats. Herein, we studied histopat...
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To date, the vast majority of intra-vital neuroimaging systems applied in clinic and diagnostics is stationary with a rigid scanning element, requires specialized facilities and costly infrastructure. Here, we describe a simple yet radical approach for optoacoustic (photoacoustic) brain imaging in vivo using a light-weight handheld probe. It enable...
Article
Unlike traditional optical methods, optoacoustic imaging is less sensitive to scattering of ballistic photons, so it is capable of high-resolution interrogation at a greater depth. By integrating video-rate visualization with multiplexing and sensing a range of endogenous and exogenous chromophores, optoacoustic imaging has matured into a versatile...
Article
Эпилепсия является одним из самых распространенных неврологических заболеваний, однако судорожные припадки не удается полностью купировать у 30% больных, что требует разработки новых фармакологических подходов к ее лечению. При некоторых патологических состояниях, в том числе фармакорезистентных формах эпилепсии, механизмы удаления глутамата из син...
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In Alzheimer’s disease (AD), tau pathology manifested by the accumulation of intraneuronal tangles and soluble toxic oligomers emerges as a promising therapeutic target. Multiple anti-tau antibodies inhibiting the formation and propagation of cytotoxic tau or promoting its clearance and degradation have been tested in clinical trials, albeit with t...
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Aging and chronic sleep deprivation (SD) are well-recognized risk factors for Alzheimer’s disease (AD), with N-methyl-D-aspartate receptor (NMDA) and downstream nitric oxide (NO) signalling implicated in the process. Herein, we investigate the impact of the age- and acute or chronic SD-dependent changes on the expression of NMDA receptor subunits (...
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The neuromuscular junction (NMJ) is the principal site for the translation of motor neurochemical signals to muscle activity. Therefore, the release and sensing machinery of acetylcholine (ACh) along with muscle contraction are two of the main targets of natural toxins and pathogens, causing paralysis. Given pharmacology and medical advances, the a...
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A celebrated American baseball player Yogi Berra notes that ‚one can observe a lot by just watching'. Along with acknowledging the fine heuristic power of visual inspection, this remark also attests to its limitations, which become critical with moving from the macroscopic world to the mesoscopic and microscopic realms. Amongst the most known pione...
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Radiation exposure can evoke cellular stress responses. Emerging recognition that long non-coding RNAs (lncRNAs) act as regulators of gene expression has broadened the spectra of molecules controlling the genomic landscape upon alterations in environmental conditions. Knowledge of the mechanisms responding to low dose irradiation (LDR) exposure is...
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The bulk of brain energy expenditure is allocated for maintenance of perpetual intrinsic activity of neurons and neural circuits. Long-term electrophysiological and neuroimaging studies in anesthetized and behaving animals show, however, that the great majority of nerve cells in the intact brain do not fire action potentials, i.e., are permanently...
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Video S4. Demonstration of 3D Reconstructed Ex Vivo Mouse Brain at 0.2-mm Increment in Rostro-caudal Axis, Related to Figure 4
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Video S6. Demonstration of 3D Reconstructed In Vivo Mouse Brain at 0.2-mm Increment in Rostro-Caudal Axis, Related to Figure 6
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Video S1. Testing of the Custom-Made Device for Mechanical Stimulation (Deflection) of Whiskers Using Magnetic Force, Related to Figures 1 and 2 An “in-house” designed electromagnetic unit was used to generate sufficient magnetic force for whisker deflections at varying frequencies.
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Video S5. Demonstration of 3D Reconstructed Ex Vivo Mouse Brain at 0.2-mm Increment in Dorsal-Ventral Axis, Related to Figure 4
Data
Video S2. Testing of the Custom-Made Device for Mechanical Stimulation (Deflection) of Whiskers Using Magnetic Force, Related to Figures 1 and 2
Data
Video S3. Testing of the Custom-Made Device for Mechanical Stimulation (Deflection) of Whiskers Using Magnetic Force, Related to Figures 1 and 2
Article
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In traditional optical imaging, limited light penetration constrains high-resolution interrogation to tissue surfaces. Optoacoustic imaging combines the superb contrast of optical imaging with deep penetration of ultrasound, enabling a range of new applications. We used multispectral optoacoustic tomography (MSOT) for functional and structural neur...
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Lidský mozek je pravděpodobně nejsložitější známá entita. Navzdory značné-mu pokroku při zkoumání a odhalování základních procesů a mechanismů vyskytujících se v mozku, zůstává naše současné chápání vyšší nervové dynamiky a funkcí poněkud neúplné. Zejména není jasné, jak neurální obvody vytvářejí smysluplné činnosti, které vedou k soudržnému vnímán...
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Published in SceinceTrends https://sciencetrends.com/the-dark-matter-of-the-brain-lights-up/ There is always more there than the eye can see. Or is there? A revolutionary chapter in the history of science was hallmarked by Galileo Galilei in 1610, looking up at the night sky through a simple telescope of his own making. What he discovered then wou...
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Changes in skin microvasculature due to external stimuli such as heating or drugs may help identify and assess vasculature dysfunction arising from a wide range of diseases. For the first time we demonstrate detailed, cross‐sectional visualization of microvascular changes through the whole skin depth in response to local heating at single vessel re...
Article
While the extensive hunt for therapeutics combating Alzheimer’s disease (AD) has fallen short of delivering effective treatments, breakthroughs towards understanding the disease mechanisms and identifying areas for future research have nevertheless been enabled. The majority of clinical trials with β- and γ-secretase modulators have been suspended...
Article
https://sciencetrends.com/?p=24605&preview=1&_ppp=181aeb0c94
Article
Synaptic transmission is a fundamental neurobiological process enabling exchange of signals between neurons as well as neurons and their non-neuronal effectors. The complex molecular machinery of the synaptic vesicle cycle and transmitter release has emerged and developed in the course of the evolutionary race, to ensure adaptive gain and survival...
Article
Deposition of amyloid plaques in limbic and associative cortices is amongst the most recognized histopathologic hallmarks of Alzheimer’s disease. Despite decades of research, there is a lack of consensus over the impact of plaques on neuronal function, with their role in cognitive decline and memory loss undecided. Evidence has emerged suggesting c...
Article
The term neuron refers to an electrically excitable cell specialized for the reception, processing, and transmission of information (electrochemical signals) throughout the nervous system and the rest of the body. Neurons are the principal structural and functional blocks of the central and peripheral nervous system empowering fast, accurate, and c...
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The aim of this study was to explore the unique imaging abilities of optoacoustic mesoscopy to visualize skin structures and microvasculature with the view of establishing a robust approach for monitoring heat‐induced hyperemia in human skin in vivo. Using raster‐scan optoacoustic mesoscopy (RSOM), we investigated whether optoacoustic (photoacousti...
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Glucose sensing is pursued extensively in biomedical research and clinical practice for assessment of the carbohydrate and fat metabolism as well as in the context of an array of disorders, including diabetes, morbid obesity, and cancer. Currently used methods for real-time glucose measurements are invasive and require access to body fluids, with n...
Article
Metabolism is a fundamental process of life. However, non-invasive measurement of local tissue metabolism is limited today by a deficiency in adequate tools for in vivo observations. We designed a multi-modular platform that explored the relation between local tissue oxygen consumption, determined by label-free optoacoustic measurements of hemoglob...
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The synaptic vesicle cycle (SVC) holds center stage in the biology of presynaptic terminals. Through recurrent exocytosis and endocytosis, it facilitates a sequence of events enabling chemical neurotransmission between functionally related neurons. As a fundamental process that links the interior of nerve cells with their environment, the SVC is al...
Article
Pain Relief With Interference ShRNA Proves Viable (https://sciencetrends.com/pain-relief-interference-shrna-proves-viable/)
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Acute and chronic trigeminal (TG) neuropathies are the cause of considerable distress, with limited treatments available at present. Nociceptive neurons enriched with the vanilloid type 1 receptor (VR1) partake in pain sensation and sensitization in the TG system. While VR1 blockers with anti-nociceptive potential are of substantial medical interes...
Article
With the central ability to visualize a variety of endogenous chromophores and biomarkers or exogenous contrast agents, optoacoustic (photoacoustic) imaging empowers new experimental capabilities for investigating brain mechanisms and functions. Here, the operational principles of optoacoustic neuroimaging are reviewed in conjunction with recent ad...
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PARTICLE (Gene PARTICL- ‘Promoter of MAT2A-Antisense RadiaTion Induced Circulating LncRNA) expression is transiently elevated following low dose irradiation typically encountered in the workplace and from natural sources. This long non-coding RNA recruits epigenetic silencers for cis-acting repression of its neighbouring Methionine adenosyltransfer...
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It has long been held that the rise of neurons as a specialized cell type also marked the onset of the grand evolutionary journey for chemical synapses. Research over recent decades has shown however that the most dynamic chapters of synaptic history have been ‘written’ out of the context of neurobiology and neuronal evolution, dating back to the e...
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Breakage of the fragile site FRA16D disrupts the WWOX (WW Domain Containing Oxidoreductase) tumor suppressor gene in osteosarcoma. However, the frequency of breakage is not sufficient to explain the rate of WWOX loss in pathogenesis. The involvement of non-coding RNA transcripts is proposed due to their accumulation at fragile sites, where they are...
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Purpose: In a pilot study, we introduce fast handheld Multi-Spectral Optoacoustic Tomography (MSOT) of the breast at 28 wavelengths, aiming to identify high-resolution optoacoustic (photoacoustic) patterns of breast cancer and non-cancerous breast tissue. Experimental design: We imaged 10 female patients aged 48-81 years with malignant non-speci...
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The long non-coding RNA PARTICLE (Gene PARTICL- ‘Promoter of MAT2A-Antisense RadiaTion Induced Circulating LncRNA) partakes in triple helix (triplex) formation, is transiently elevated following low dose irradiation and regulates transcription of its neighbouring gene - Methionine adenosyltransferase 2A. It now emerges that PARTICLE triplex sites a...