A5032207650- Neuroscience and Neuropharmacology Research
- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurogenesis and neuroplasticity mechanisms
- Proteoglycans and glycosaminoglycans research
- Neuropeptides and Animal Physiology
- Receptor Mechanisms and Signaling
- Circadian rhythm and melatonin
- Sleep and Wakefulness Research
- Trace Elements in Health
- Cholesterol and Lipid Metabolism
- Mitochondrial Function and Pathology
- Genetics and Neurodevelopmental Disorders
- RNA Interference and Gene Delivery
- Signaling Pathways in Disease
- Supramolecular Self-Assembly in Materials
- S100 Proteins and Annexins
- Immune cells in cancer
- Cholinesterase and Neurodegenerative Diseases
- Prion Diseases and Protein Misfolding
- HIV Research and Treatment
- Immune Response and Inflammation
- HIV-related health complications and treatments
- Pharmacological Receptor Mechanisms and Effects
- NF-κB Signaling Pathways
Massachusetts Institute of Technology
2021-2024
Georgetown University
2017-2020
Georgetown University Medical Center
2018-2020
Georgetown-Howard Universities Center for Clinical and Translational Science
2019
National Institutes of Health
2017
George Mason University
2014
Memory disruption in mild cognitive impairment (MCI) and Alzheimer's disease (AD) is poorly understood, particularly at early stages preceding neurodegeneration. In mouse models of AD, there are disruptions to sharp wave ripples (SWRs), hippocampal population events with a critical role memory consolidation. However, the microcircuitry underlying these under-explored. We tested whether selective reduction parvalbumin-expressing (PV) inhibitory interneuron activity underlies hyperactivity SWR...
Recent increases in human longevity have been accompanied by a rise the incidence of dementia, highlighting need to preserve cognitive function an aging population. A small percentage individuals with pathological hallmarks neurodegenerative disease are able maintain normal cognition. Although molecular mechanisms that govern this neuroprotection remain unknown, exhibit resilience (CgR) represent unique source therapeutic insight. For both humans and animal models, living enriched,...
DNA double-strand breaks (DSBs) are linked to neurodegeneration and senescence. However, it is not clear how DSB-bearing neurons influence neuroinflammation associated with neurodegeneration. Here, we characterize from the CK-p25 mouse model of using single-nucleus, bulk, spatial transcriptomic techniques. enter a late-stage damage response marked by nuclear factor κB (NFκB)-activated senescent antiviral immune pathways. In humans, Alzheimer's disease pathology closely activation in...
Demyelination is a common pathological feature in wide range of diseases, characterized by the loss myelin sheath and myelin-supporting oligodendrocytes. These losses lead to impaired axonal function, increased vulnerability axons damage, result significant brain atrophy neuro-axonal degeneration. Multiple pathomolecular processes contribute neuroinflammation, oligodendrocyte cell death, progressive neuronal dysfunction. In this study, we use cuprizone mouse model demyelination investigate...
Hippocampal sharp wave ripples (SWRs) represent irregularly occurring synchronous neuronal population events that are observed during phases of rest and slow sleep. SWR activity follows learning involves sequential replay training-associated assemblies is critical for systems level memory consolidation. SWRs initiated by CA2 or CA3 pyramidal cells (PCs) require initial excitation CA1 PCs as well participation parvalbumin (PV) expressing fast spiking (FS) inhibitory interneurons. These...
Drugs that target monoaminergic transmission represent a first-line treatment for major depression. Though full understanding of the mechanisms underlie antidepressant efficacy is lacking, evidence supports role enhanced excitatory transmission. This can occur through two non-mutually exclusive mechanisms. The first involves increased function neurons relatively direct such as dendritic arborization. Another mechanism reduced inhibitory function, which occurs with rapid ketamine. Consistent...
Disruptions to daily living, inflammation, and astrogliosis are characteristics of Alzheimer's disease. Thus, circadian rhythms, nest construction, IL-1β TNF-α, glial fibrillary acidic protein (GFAP) were examined in a mouse model developed late-onset disease-the most common form the Mice carrying both mutated human AβPP transgene found CRND8 apolipoprotein E ε4 allele (CRND8/E4) compared with mice wildtype (WT) mice. Circadian rhythms evaluated by wheel-running behavior. Activity living was...
Much of the research in Alzheimer's disease (AD) that uses mouse models focuses on early-onset form disease, which accounts for less than 5% cases. In contrast, this study used a late-onset AD model to examine interaction between increased dietary zinc (Zn) and apolipoprotein E (ApoE) gene. ApoE ε4 is overrepresented enhances Zn binding amyloid-β (Aβ). This sought determine if elevated would impair spatial memory CRND8 mice (CRND8), as well who carry both mutated human amyloid precursor...
Abstract The HIV‐1 protein Tat is continually released by HIV‐infected cells despite effective combination antiretroviral therapies (cART). promotes neurotoxicity through enhanced expression of proinflammatory molecules from resident and infiltrating immune cells. These include matrix metalloproteinases (MMPs), which are pathologically elevated in HIV, known to drive central nervous system (CNS) injury varied disease settings. A subset MMPs can activate G‐protein coupled protease‐activated...
Matrix metalloproteinases (MMPs) are a family of enzymes that typically released from intracellular stores to act on specific extracellular substrates. MMP expression and activity can be increased in neuronal activity-dependent manner, further response tissue injury. substrates include cell adhesion molecules (CAMs) abundantly expressed the brain well positioned for membrane proximal cleavage. Importantly, CAM integrity is important synaptic structure axon-myelin interactions, shed...
Abstract Microglia are in a privileged position to both affect and be affected by neuroinflammation, neuronal activity injury, which all hallmarks of seizures the epilepsies. Hippocampal microglia become activated after prolonged, damaging known as status epilepticus (SE). However, since SE causes hyperactivity injury neurons, mechanisms triggering this activation remain unclear, does relevance microglial ensuing epileptogenic processes. In study, we use electroconvulsive shock (ECS) study...
Summary Apolipoprotein E4 (APOE4) is the greatest known genetic risk factor for developing late- onset Alzheimer’s disease and its expression in microglia associated with pro- inflammatory states. How interaction of APOE4 neurons differs from expressing disease-neutral allele APOE3 currently unknown. Here, we employ CRISPR-edited induced pluripotent stem cells (iPSCs) to dissect impact neuron-microglia communication. Our results reveal that induces a distinct metabolic program marked by...
Abstract Hippocampal sharp wave ripples (SWRs) represent irregularly occurring synchronous neuronal population events that are observed during phases of rest and slow sleep. SWR activity follows learning involves sequential replay training-associated assemblies is critical for systems level memory consolidation. SWRs initiated by CA2 or CA3 pyramidal cells require initial excitation CA1 as well subsequent participation parvalbumin (PV) expressing fast spiking (FS) inhibitory interneurons....
Abstract Drugs that target monoaminergic transmission represent a first-line treatment for major depression. Though full understanding of the mechanisms underlie antidepressant efficacy is lacking, evidence supports role enhanced excitatory transmission. This can occur through two non-mutually exclusive mechanisms. The first involves increased function neurons relatively direct such as dendritic arborization. Another mechanism reduced inhibitory function, which occurs with rapid ketamine....
Abstract Memory disruption in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) is poorly understood, particularly at early stages preceding neurodegeneration. In mouse models of AD, there are disruptions to sharp wave ripples (SWRs), hippocampal population events with a critical role memory consolidation. However, the micro-circuitry underlying these under-explored. We tested if selective reduction parvalbumin-expressing (PV) inhibitory interneuron activity underlies...
OBJECTIVES/SPECIFIC AIMS: Alzheimer’s disease (AD) is the leading cause of dementia, and a rapidly growing public health crisis as life expectancy increases. Two hallmark symptoms are memory impairment pathological accumulation amyloid beta protein. The hippocampus brain region critical for consolidation new memories, one first regions in which observed. Our lab others have observed disruption to hippocampal network activity that amyloid-accumulating mice. However, mechanisms neuronal...