A5005178068- Neuroinflammation and Neurodegeneration Mechanisms
- Alzheimer's disease research and treatments
- Tryptophan and brain disorders
- Cerebrospinal fluid and hydrocephalus
- Clusterin in disease pathology
- Spinal Dysraphism and Malformations
- Traumatic Brain Injury Research
- Neurological Disease Mechanisms and Treatments
- Reproductive System and Pregnancy
- Inflammation biomarkers and pathways
- Inflammasome and immune disorders
- Medicinal Plants and Bioactive Compounds
- Zebrafish Biomedical Research Applications
- Diverse Music Education Insights
- Ferroptosis and cancer prognosis
- Immune Response and Inflammation
- IL-33, ST2, and ILC Pathways
- Adolescent and Pediatric Healthcare
- Neonatal Respiratory Health Research
- Neurological Disorders and Treatments
- Mitochondrial Function and Pathology
- Heme Oxygenase-1 and Carbon Monoxide
- Anesthesia and Neurotoxicity Research
- Diet and metabolism studies
- COVID-19 Impact on Reproduction
Stanford University
2023-2025
University of Virginia
2019-2024
Palo Alto University
2023
Alzheimer’s Disease Neuroimaging Initiative
2023
Union Bank of Switzerland
2023
Salisbury University
2019
Abstract Traumatic brain injury (TBI) is a leading global cause of death and disability. Here we demonstrate in an experimental mouse model TBI that mild forms trauma severe deficits meningeal lymphatic drainage begin within hours last out to at least one month post-injury. To investigate mechanism underlying impaired function TBI, examined how increased intracranial pressure (ICP) influences the lymphatics. We ICP can contribute dysfunction. Moreover, show pre-existing dysfunction before...
Recent studies have begun to reveal critical roles for the brain's professional phagocytes, microglia, and their receptors in control of neurotoxic amyloid beta (Aβ) myelin debris accumulation neurodegenerative disease. However, intracellular molecules that orchestrate neuroprotective functions microglia remain poorly understood. In our studies, we find targeted deletion SYK leads exacerbated Aβ deposition, aggravated neuropathology, cognitive defects 5xFAD mouse model Alzheimer's disease...
Impaired cerebral glucose metabolism is a pathologic feature of Alzheimer's disease (AD), with recent proteomic studies highlighting disrupted glial in AD. We report that inhibition indoleamine-2,3-dioxygenase 1 (IDO1), which metabolizes tryptophan to kynurenine (KYN), rescues hippocampal memory function mouse preclinical models AD by restoring astrocyte metabolism. Activation astrocytic IDO1 amyloid β and tau oligomers increases KYN suppresses glycolysis an aryl hydrocarbon...
Emerging evidence suggests that the meningeal compartment plays instrumental roles in various neurological disorders, however, we still lack fundamental knowledge about biology. Here, utilized high-throughput RNA sequencing (RNA-seq) techniques to investigate transcriptional response of meninges traumatic brain injury (TBI) and aging sub-acute chronic time frames. Using single-cell (scRNA-seq), first explored how mild TBI affects cellular landscape young mice at one-week post-injury. Then,...
Mutations in INPP5D, which encodes for the SH2-domain-containing inositol phosphatase SHIP-1, have recently been linked to an increased risk of developing late-onset Alzheimer's disease. While INPP5D expression is almost exclusively restricted microglia brain, little known regarding how SHIP-1 affects neurobiology or neurodegenerative disease pathogenesis.
After a generation of failed therapies, microglia have captivated scientists searching for unexplored avenues to treat neurodegenerative diseases. The last decade research has unveiled remarkable capacity alter the trajectory neurodegeneration through interaction these brain-resident immune cells with disease pathology and other disease-associated cell types in brain. Emerging from this collective work is idea that can play both neuroprotective deleterious roles neurological pathogenesis....
Variants in the CLUSTERIN gene have been identified as a risk factor for late-onset Alzheimer's disease and are linked to decreased white matter integrity healthy adults. However, specific role clusterin myelin maintenance context of remains unclear. We employed combination immunofluorescence transmission electron microscopy techniques, primary culture OPCs, an animal model disease. found that phagocytosis debris such amyloid beta, myelin, apoptotic cells, increases expression...
Abstract INTRODUCTION While immune dysfunction has been increasingly linked to Alzheimer's disease (AD) progression, many major innate signaling molecules have yet be explored in AD pathogenesis using genetic targeting approaches. METHODS To investigate a role for the key adaptor molecule, stimulator of interferon genes (STING), AD, we deleted Sting1 5xFAD mouse model AD‐related amyloidosis and evaluated effects on pathology, neuroinflammation, gene expression, cognition. RESULTS Genetic...
Recent advances have highlighted the importance of several innate immune receptors expressed by microglia in Alzheimer’s disease (AD). In particular, mounting evidence from AD patients and experimental models indicates pivotal roles for TREM2, CD33, CD22 neurodegenerative progression. While there is growing interest targeting these microglial to treat AD, we still lack knowledge downstream signaling molecules used orchestrate responses AD. Notably, been described influence associated with...
Abstract Traumatic brain injury (TBI) has emerged as a leading cause of death and disability. Despite being growing medical issue, the biological factors that promote central nervous system (CNS) pathology neurological dysfunction following TBI remain poorly characterized. Recently, meningeal lymphatic was identified critical mediator drainage from CNS. In comparison to other peripheral organs, our understanding how defects in CNS contribute disease is limited. It still unknown impacts...
Perturbations to the in utero environment can dramatically change trajectory of offspring neurodevelopment. Insults commonly encountered modern human life such as infection, toxins, high-fat diet, prescription medications, and others are increasingly linked behavioral alterations prenatally-exposed offspring. While appreciation is expanding for potential consequence that these triggers have on embryo development, there a paucity information concerning how crucial maternal-fetal interface...
Abstract White matter loss has been described as a common occurrence in Alzheimer’s disease (AD) patients for multiple decades. However, it remains unclear why oligodendrocyte progenitor cells (OPCs) fail to repair myelin deficits these patients. Here, we show that clusterin, risk factor late-onset AD, is produced by OPCs and inhibits their differentiation into oligodendrocytes. Specifically, demonstrate unique subset of produces clusterin. We phagocytosis debris, including amyloid beta (Aβ)...
Impaired cerebral glucose metabolism is a pathologic feature of Alzheimer Disease (AD), and recent proteomic studies highlight disruption glial carbohydrate with disease progression. Here, we report that inhibition indoleamine-2,3-dioxygenase 1 (IDO1), which metabolizes tryptophan to kynurenine (KYN) in the first step pathway, rescues hippocampal memory function plasticity preclinical models amyloid tau pathology by restoring astrocytic metabolic support neurons. Activation IDO1 astrocytes...
Diabetes mellitus-induced hyperglycemia is associated with a number of pathologies such as retinopathy, nephropathy, delayed wound healing, and diabetic peripheral neuropathy (DPN). Approximately 50% patients diabetes mellitus will develop DPN, which characterized by disrupted sensory and/or motor functioning, treatment limited to pain management. Zebrafish ( Danio rerio) are an emerging animal model used study metabolic disorders, including diabetes. Diabetic healing have all been...
ABSTRACT Traumatic brain injury (TBI) has emerged as a leading cause of death and disability. Despite being growing medical issue, the biological factors that promote central nervous system (CNS) pathology neurological dysfunction following TBI remain poorly characterized. Recently, meningeal lymphatic was identified critical mediator drainage from CNS. In comparison to other peripheral organs, our understanding how defects in CNS contribute disease is limited. It still unknown impacts...
SUMMARY Human genetics implicate defective myeloid responses in the development of late onset, age-associated Alzheimer’s disease (AD). Aging is characterized by a decline metabolism that triggers maladaptive, neurotoxic immune responses. TREM1 an amplifier pro-inflammatory responses, and here we find Trem1 deficiency prevents age-dependent changes metabolism, inflammation, hippocampal memory function. rescues declines ribose-5P, glycolytic intermediate precursor for purine, pyrimidine, NAD...
<title>Abstract</title> Background: White matter loss is a well-documented phenomenon in Alzheimer's disease (AD) patients that has been recognized for decades. However, the underlying reasons failure of oligodendrocyte progenitor cells (OPCs) to repair myelin deficits these remain elusive. A single nucleotide polymorphism (SNP) Clusterin identified as risk factor late-onset and linked decrease white integrity healthy adults, but its specific role function maintenance Alzheimer’s pathology...
Systemic maternal inflammation during pregnancy is increasingly thought to be a risk factor for development of autism spectrum disorder (ASD), which diagnosed at rate 4-fold higher in males than females. Administration the viral mimic polyI:C pregnant mice mid-gestation leads ASD-related phenotypes offspring, consisting deficits communication and socialization, as well repetitive behaviors. In this model immune activation (MIA), elevated production serum cytokines known promote alterations...