Publications by authors named "Lik Wei Wong"

Sleep is vital for maintaining physical and mental well-being, impacting cognitive functions like memory and learning through neuroplasticity. Sleep disturbances prevalent in neurological and psychiatric disorders exacerbate cognitive decline, imposing societal burdens. Exploring the relationship between sleep and neuroplasticity elucidates the mechanisms influencing cognition, particularly amidst the prevalent sleep disturbances in these clinical populations.

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Age-induced impairments in learning and memory are in part caused by changes to hippocampal synaptic plasticity during aging. The p75 neurotrophin receptor (p75 ) and mechanistic target of rapamycin (mTOR) are implicated in synaptic plasticity processes. mTOR is also well known for its involvement in aging.

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Practical classes are critical instructional activities in facilitating learning and motivation in health sciences education. With increasing pedagogical activities being conducted in virtual or remote settings, this study assessed how a remote practical assisted by physiological monitoring smartphone applications impacted student motivation and the achievement of intended learning outcomes in exercise physiology teaching. A total of 24 students (out of 30; 80%) were surveyed via a mixed-methods questionnaire containing 27 closed-ended, and 3 the traditional in-class practical in randomized order.

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We recently nominated cytokine signaling through the Janus-kinase-signal transducer and activator of transcription (JAK/STAT) pathway as a potential AD drug target. As hydroxychloroquine (HCQ) has recently been shown to inactivate STAT3, we hypothesized that it may impact AD pathogenesis and risk. Among 109,124 rheumatoid arthritis patients from routine clinical care, HCQ initiation was associated with a lower risk of incident AD compared to methotrexate initiation across 4 alternative analyses schemes addressing specific types of biases including informative censoring, reverse causality, and outcome misclassification (hazard ratio [95% confidence interval] of 0.

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Synaptic plasticity in the hippocampal Cornu Ammonis (CA) subfield, CA2, is tightly regulated. However, CA2 receives projections from several extra-hippocampal modulatory nuclei that release modulators that could serve to fine-tune plasticity at CA2 synapses. Considering that there are afferent projections from the serotonergic median raphe to hippocampal CA2, we hypothesized that the neuromodulator serotonin (5-hydroxytryptamine; 5-HT) could modulate CA2 synaptic plasticity.

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Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by memory loss and cognitive decline. Synaptic impairment is one of the first events to occur in the progression of this disease. Synaptic plasticity and cellular association of various plastic events have been shown to be affected in AD models.

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The amygdala is known to modulate hippocampal synaptic plasticity. One role could be an immediate effect of basolateral amygdala (BLA) in priming synaptic plasticity in the hippocampus. Another role could be through associative synaptic co-operation and competition that triggers events involved in the maintenance of synaptic potentiation.

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Aging and age-related neurodegenerative diseases have become one of the major concerns in modern times as cognitive abilities tend to decline when we get older. It is well known that the main cause of this age-related cognitive deficit is due to aberrant changes in cellular, molecular circuitry and signaling pathways underlying synaptic plasticity and neuronal connections. The p75 neurotrophin receptor (p75) is one of the important mediators regulating the fate of the neurons in the nervous system.

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The plasticity mechanisms in the nervous system that are important for learning and memory are greatly impacted during aging. Notably, hippocampal-dependent long-term plasticity and its associative plasticity, such as synaptic tagging and capture (STC), show considerable age-related decline. The p75 neurotrophin receptor (p75 ) is a negative regulator of structural and functional plasticity in the brain and thus represents a potential candidate to mediate age-related alterations.

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A prevalent model of Alzheimer's disease (AD) pathogenesis postulates the generation of neurotoxic fragments derived from the amyloid precursor protein (APP) after its internalization to endocytic compartments. The molecular pathways that regulate APP internalization and intracellular trafficking in neurons are incompletely understood. Here, we report that 5xFAD mice, an animal model of AD, expressing signaling-deficient variants of the p75 neurotrophin receptor (p75 ) show greater neuroprotection from AD neuropathology than animals lacking this receptor.

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The blood-brain barrier (BBB) tightly controls the molecular exchange between the brain parenchyma and blood. Accumulated evidence from transgenic animal Alzheimer's disease (AD) models and human AD patients have demonstrated that BBB dysfunction is a major player in AD pathology. In this review, we discuss the role of the BBB in maintaining brain integrity and how this is mediated by crosstalk between BBB-associated cells within the neurovascular unit (NVU).

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Sleep plays an important role in the establishment of long-term memory; as such, lack of sleep severely impacts domains of our health including cognitive function. Epigenetic mechanisms regulate gene transcription and protein synthesis, playing a critical role in the modulation of long-term synaptic plasticity and memory. Recent evidences indicate that transcriptional dysregulation as a result of sleep deprivation (SD) may contribute to deficits in plasticity and memory function.

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The CD137-CD137 ligand (CD137L) costimulatory system is a critical immune checkpoint with pathophysiological implications in autoimmunity. In this study, we investigated the role of CD137L-mediated costimulation on renal, cutaneous and cerebral manifestations in lupus and the underlying immunological mechanism. Lupus-prone C57BL/6 (B6.

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Sleep deprivation (SD) interferes with hippocampal structural and functional plasticity, formation of long-term memory and cognitive function. The molecular mechanisms underlying these effects are incompletely understood. Here, we show that SD impaired synaptic tagging and capture and behavioral tagging, two major mechanisms of associative learning and memory.

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Aberrant function of the RNA-binding protein TDP-43 has been causally linked to multiple neurodegenerative diseases. Due to its large number of targets, the mechanisms through which TDP-43 malfunction cause disease are unclear. Here, we report that knockdown, aggregation, or disease-associated mutation of TDP-43 all impair intracellular sorting and activity-dependent secretion of the neurotrophin brain-derived neurotrophic factor (BDNF) through altered splicing of the trafficking receptor Sortilin.

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GABAA receptors are pentameric ligand-gated ion channels that mediate inhibitory fast synaptic transmission in the central nervous system. Consistent with recent pentameric ligand-gated ion channels structures, sequence analysis predicts an α-helix near the N-terminus of each GABAA receptor subunit. Preceding each α-helix are 8-36 additional residues, which we term the N-terminal extension.

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The GABAC receptor and closely related GABAA receptor are members of the pentameric ligand-gated ion channels (pLGICs) superfamily and mediate inhibitory fast synaptic transmission in the nervous system. Each pLGIC subunit comprises an N-terminal extracellular agonist-binding domain followed by a channel domain and a variable intracellular domain. Available structural information shows that the core of the agonist-binding domain is a β sandwich of ten β-strands, which form the agonist-binding pocket at the subunit interface.

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