Publications by authors named "Moy S"

Perineuronal nets (PNNs) are a specialized extracellular matrix that surround certain populations of neurons, including (inhibitory) parvalbumin (PV) expressing-interneurons throughout the brain and (excitatory) CA2 pyramidal neurons in hippocampus. PNNs are thought to regulate synaptic plasticity by stabilizing synapses and as such, could regulate learning and memory. Most often, PNN functions are queried using enzymatic degradation with chondroitinase, but that approach does not differentiate PNNs on CA2 neurons from those on adjacent PV cells.

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Perineuronal nets (PNNs) are a specialized extracellular matrix that surround certain populations of neurons, including (inhibitory) parvalbumin (PV) expressing-interneurons throughout the brain and (excitatory) CA2 pyramidal neurons in hippocampus. PNNs are thought to regulate synaptic plasticity by stabilizing synapses and as such, could regulate learning and memory. Most often, PNN functions are queried using enzymatic degradation with chondroitinase, but that approach does not differentiate PNNs on CA2 neurons from those on adjacent PV cells.

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  • Traumatic social experiences impact behavior by enhancing survival and safety, but how the brain's networks regulate these changes is not well understood.* -
  • Researchers combined traditional and modern techniques to track mouse behaviors during social threat learning, discovering new movements that reveal alterations in social motivation.* -
  • Analysis of brain activity showed significant changes in several key regions when mice recognized a social threat, indicating that altered brain connectivity is important for modifying behavior in response to such threats.*
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  • Researchers explored the connection between heavy alcohol use and obesity as midlife risk factors for late-onset Alzheimer's disease (LOAD), uncovering a link to disrupted lipophagy and lysosomal function.
  • The study found that the loss of lysosomal acid lipase (LAL) in neurons leads to the accumulation of neuronal lysosomal lipids (NLL), which interferes with the clearance of amyloid-beta (Aβ), a key component of Alzheimer's pathology.
  • As LAL levels decline with age in both mice and humans, its reduction is associated with increased Aβ and cognitive deficits, highlighting the importance of maintaining LAL function to potentially mitigate Alzheimer's risk as we age.
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  • Autism Spectrum Disorder (ASD) is primarily seen in males and is marked by difficulties in communication and social behaviors, which this study examined using a mouse model.* -
  • The research utilized various sequencing techniques to discover differences in gene expression and methylation patterns in the amygdala of two mouse strains, revealing potential links to sociability deficits.* -
  • Results indicated that altered immune-related processes and oligodendrocyte/microglia differentiation were associated with ASD traits, highlighting the need for further research into these mechanisms and the effects of oxytocin.*
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  • Sleep disruption and Tau accumulation are linked to cognitive decline in Alzheimer's disease, but the relationship between them is not fully understood.
  • In a study using PS19 mice, early-onset hyperarousal and selective sleep disruption were observed, with significant memory decline due to chronic sleep disruption occurring in males.
  • Despite earlier hyperarousal in females, they showed more resilience in cognitive decline compared to males, indicating potential sex-specific differences in the effects of sleep disruption on cognitive health.
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Purpose: Artificial intelligence (AI) technology is being rapidly adopted into many different branches of medicine. Although research has started to highlight the impact of AI on health care, the focus on patient perspectives of AI is scarce. This scoping review aimed to explore the literature on adult patients' perspectives on the use of an array of AI technologies in the health care setting for design and deployment.

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  • Sleep disruption is common in aging and neurodegenerative diseases like Alzheimer's, contributing to cognitive decline and AD progression, making better sleep treatments necessary.
  • Current sleep medications can increase the risk of AD, prompting researchers to explore alternatives like the endocannabinoid system and fatty acid amide hydrolase (FAAH) as potential sleep aids.
  • While inhibiting FAAH showed short-term benefits for sleep in a model of Tauopathy, knockout studies indicated that completely disabling FAAH may not be beneficial for overall sleep health or cognitive function.
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  • Autism Spectrum Disorder (ASD) is linked to communication and social behavior challenges, with this study exploring the underlying brain mechanisms and sex differences in ASD using mouse models.
  • Research involved measuring sociability in mice, analyzing gene expression changes, and identifying differentially methylated genes related to immune processes in the amygdala.
  • Results showed significant differences in social behavior and brain activity between mouse strains, including impaired myelination linked to ASD, with potential therapeutic insights regarding oxytocin, but further studies are needed to clarify these cellular mechanisms.
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  • - Sex differences in stress-related neuropsychiatric disorders, influenced by glucocorticoids (stress hormones), are not well understood, but research on glucocorticoid and mineralocorticoid receptors reveals important findings.
  • - Knockout mice studies show that loss of these receptors affects anxiety, behavior, and sociability differently in males and females, indicating sex-specific roles in stress adaptation and fear response.
  • - Global gene analysis highlights significant dysregulation in female mice lacking both receptors, suggesting that GR and MR imbalances lead to distinct molecular changes in the hippocampus, with implications for treating stress-related disorders across genders.
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  • Glyphosate, a common herbicide, targets the shikimate pathway in plants and affects gut microbiota, which can potentially disrupt the gut-brain axis and lead to neurological issues.
  • In a study, mice were exposed to two different doses of glyphosate over time; neurobehavioral changes were minimal, but significant alterations in fecal metabolites were observed, especially in aromatic amino acids at higher doses.
  • The research concluded that even at high levels of glyphosate, there was little evidence of impairment in the gut-brain axis, suggesting that neurotoxicity and gut microbiota changes may not be as pronounced as initially thought.
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  • TDP-43 proteinopathies, such as frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS), are neurodegenerative diseases where the protein TDP-43 misfolds and disrupts neuronal function.
  • Researchers created models that mimic sporadic TDP-43 proteinopathy, showing how acetylation at lysine 145 impairs TDP-43's ability to bind RNA and leads to gene mis-regulation.
  • Results indicate that this acetylation triggers harmful changes in neurons, evidenced by cognitive decline and altered gene expression related to synaptic function, mirroring characteristics seen in human FTLD cases.
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Neurodevelopmental disorders (NDDs) are complex conditions characterized by heterogeneous clinical profiles and symptoms that arise in infancy and childhood. NDDs are often attributed to a complicated interaction between genetic risk and environmental factors, suggesting a need for preclinical models reflecting the combined impact of heritable susceptibility and environmental effects. A notable advantage of "two-hit" models is the power to reveal underlying vulnerability that may not be detected in studies employing only genetic or environmental alterations.

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Mitosis is an essential process in which the duplicated genome is segregated equally into two daughter cells. CTCF has been reported to be present in mitosis and has a role in localizing CENP-E, but its importance for mitotic fidelity remains to be determined. To evaluate the importance of CTCF in mitosis, we tracked mitotic behaviors in wild-type and two different CTCF CRISPR-based genetic knockdowns.

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  • Sleep disruption is linked to neurodegenerative diseases like Alzheimer's, where impaired synaptic processes may contribute to cognitive decline, particularly through Tau protein aggregation.
  • A study using transgenic mice revealed that PS19 mice experience early loss of sleep during the dark phase, with females showing symptoms earlier than males.
  • Although sleep disruption did not increase Tau pathology in the brain, chronic sleep loss was found to worsen spatial memory decline specifically in male mice.
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Mitosis is an essential process in which the duplicated genome is segregated equally into two daughter cells. CTCF has been reported to be present in mitosis but its importance for mitotic fidelity remains to be determined. To evaluate the importance of CTCF in mitosis, we tracked mitotic behaviors in wild type and two different CTCF CRISPR-based genetic knockdowns.

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  • Acetylcholine (ACh) signaling changes have been linked to several neurological diseases, and ACh neurons in the brain also release GABA, but the role of GABA in ACh signaling is not fully understood.
  • This study aimed to explore how the elimination of GABA co-transmission from ACh neurons impacted mouse behaviors, using genetically modified mice that specifically lacked the ability to co-release GABA.
  • The results showed that while basic functions like sociability and motor skills remained unchanged, the loss of GABA co-transmission significantly impaired social, spatial, and fear memory, indicating that ACh/GABA interactions are important for higher cognitive processes.
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  • Behavioral phenotyping in neonatal mice helps researchers study how early changes in brain development relate to human neurodevelopmental disorders.
  • This chapter outlines a testing method that assesses mice behavior while reducing stress for the pups and their mothers.
  • Testing starts when mice are 6-8 days old and includes various evaluations up to 20-21 days, focusing on different behavioral traits like movement and reflexes.
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  • Patients with autism spectrum disorder (ASD) experience significant sleep disruptions early in life, which may have lasting developmental effects; researchers investigated this in mice with a SHANK3 gene mutation linked to ASD.
  • They recorded sleep patterns in Shank3 mutated mice and wild-type siblings, exposing them to early life sleep disruption and comparing various behavioral outcomes later in adulthood.
  • Results showed that Shank3 mice slept less and exhibited distinct behavioral changes based on sex and early life sleep disruption, whereas wild-type mice appeared resilient, highlighting potential long-term consequences of sleep issues in genetically vulnerable populations.
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Introduction: Pain management after elective, unilateral total hip and knee arthroplasty (THA and TKA) should use a multimodal approach. At discharge, challenges include ensuring correct prescribing practices to optimise analgesia and rationalise opioid use as well as ensuring patients are adequately educated to take these medications safely and effectively in the community. This audit cycle reports on a prescriber and patient education intervention using printed guidelines, educational outreach and prescription standardisation along with a patient information sheet to address the high unplanned readmission rate following THA and TKA at our institution.

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  • Heavy alcohol use in adolescence is linked to an increased risk of Alzheimer's disease (AD), but the specific mechanisms connecting the two remain unclear.
  • A study using a mouse model showed that binge drinking during adolescence led to heightened levels of toxins associated with AD and increased inflammation in the brain, particularly in females.
  • Treatment with the anti-inflammatory drug minocycline during the binge drinking period mitigated some of the harmful effects, including increased anxiety and memory loss, suggesting that inflammation plays a critical role in these changes.
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  • * A set of key genes, including Usp11 and Wars2, was found to be altered in these mice at different ages, with CHD8 shown to directly interact with their genetic regions.
  • * Older Chd8 mice exposed to DM also exhibited more severe symptoms and changes in gene expression related to vascular health, highlighting how genetic factors and environmental influences together shape autism-related traits throughout development.
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Drug-drug interaction (DDI) is an important consideration for clinical decision making in prostate cancer treatment. The objective of this study was to evaluate the effect of enzalutamide, an oral androgen receptor inhibitor, on the pharmacokinetics (PK) of digoxin (P-glycoprotein [P-gp] probe substrate) and rosuvastatin (breast cancer resistance protein [BCRP] probe substrate) in men with metastatic castration-resistant prostate cancer (mCRPC). This was a phase I, open-label, fixed-sequence, crossover study (NCT04094519).

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Background: Following the successful Perioperative Surgical Home (PSH) practice for total knee arthroplasty (TKA) at our institution, the need for continuous improvement was realized, including the deimplementation of antiquated PSH elements and introduction of new practices.

Aim: To investigate the transition from femoral nerve blocks (FNB) to adductor canal nerve blocks (ACB) during TKA.

Methods: Our 13-month study from June 2016 to 2017 was divided into four periods: a three-month baseline (103 patients), a one-month pilot (47 patients), a three-month implementation and hardwiring period (100 patients), and a six-month evaluation period (185 patients).

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Neurologic disorders often disproportionately affect specific brain regions, and different apoptotic mechanisms may contribute to white matter pathology in leukodystrophies or gray matter pathology in poliodystrophies. We previously showed that neural progenitors that generate cerebellar gray matter depend on the anti-apoptotic protein BCL-xL. Conditional deletion of Bcl-xL in these progenitors produces spontaneous apoptosis and cerebellar hypoplasia, while similar conditional deletion of Mcl-1 produces no phenotype.

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