A5048974123- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neuropharmacology Research
- Neurogenesis and neuroplasticity mechanisms
- Immune cells in cancer
- Nerve injury and regeneration
- Tryptophan and brain disorders
- MicroRNA in disease regulation
- Neurological Disease Mechanisms and Treatments
- Chemokine receptors and signaling
- Immune Response and Inflammation
- Anesthesia and Neurotoxicity Research
- Photoreceptor and optogenetics research
- Neural dynamics and brain function
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Neuropeptides and Animal Physiology
- Proteoglycans and glycosaminoglycans research
- Platelet Disorders and Treatments
- Autism Spectrum Disorder Research
- Receptor Mechanisms and Signaling
- NF-κB Signaling Pathways
- Cell Adhesion Molecules Research
- Nuclear Receptors and Signaling
University of California, Los Angeles
2018-2025
Johns Hopkins University
2007-2020
National Institute on Drug Abuse
2017-2020
National Institutes of Health
2017-2020
Johns Hopkins Medicine
2011-2017
The mammalian CNS contains an abundant, widely distributed population of glial cells that serve as oligodendrocyte progenitors. It has been reported these NG2-immunoreactive (NG2 + cells) form synapses and generate action potentials, suggesting neural-evoked excitation progenitors may regulate oligodendrogenesis. However, recent studies also suggest NG2 are comprised functionally distinct groups differ in their ability to respond neuronal activity, undergo differentiation, experience injury...
Structural plasticity of dendritic spines and synapses is a fundamental mechanism governing neuronal circuits may form an enduring basis for information storage in the brain. We find that p65 subunit nuclear factor-κB (NF-κB) transcription factor, which required learning memory, controls excitatory synapse spine formation morphology murine hippocampal neurons. Endogenous NF-κB activity elevated by transmission during periods rapid development. During vitro synaptogenesis, enhances density...
Oligodendrocyte precursor cells (OPCs) express NMDA receptors (NMDARs) and form synapses with glutamatergic neurons throughout the CNS. Although glutamate influences proliferation maturation of these progenitors in vitro , role NMDAR signaling oligodendrogenesis myelination vivo is not known. Here, we investigated consequences genetically deleting obligatory subunit NR1 from OPCs their oligodendrocyte progeny CNS developing mature mice. NMDAR-deficient proliferated normally, achieved...
Astrocytes are ubiquitous CNS cells that support tissue homeostasis through ion buffering, neurotransmitter recycling, and regulation of vasculature. Yet, despite the essential functional roles they fill, very little is known about physiology astrocytes in ventral midbrain, a region houses dopamine-releasing neurons critical for reward learning motivated behaviors. Here, using combination whole-transcriptome sequencing, histology, slice electrophysiology, calcium imaging, we performed first...
During aging, microglia produce inflammatory factors, show reduced tissue surveillance, altered interactions with synapses, and prolonged responses to CNS insults, positioning these cells have profound impact on the function of nearby neurons. We others recently showed that microglial attributes differ significantly across brain regions in young adult mice. However, degree which properties vary during aging is largely unexplored. Here, we analyze manipulate within basal ganglia, circuits...
Significance Parkinson’s disease (PD) is a chronic dopamine (DA) neuron degenerative disorder. Little known about factors that impact vulnerability of DA neurons to pathological insults. In this study, we found vesicular glutamate transporter 2 (VgluT2) expression may play an important role in protecting neurons. Selective deletion VgluT2 led significant reduction brain-derived neurotrophic factor and its receptor tyrosine kinase B increase death caused by the neurotoxin...
Abstract Synapse dysfunction is tightly linked to cognitive changes during aging, but underlying mechanisms driving are minimally understood. The extracellular matrix (ECM) can potently regulate synapse integrity and plasticity. Yet the status of brain ECM aging remains virtually unexplored. Using novel ECM-optimized proteomic workflows, we discovered striking regional differences in composition aging-induced remodeling. was also aligned with preserved protein abundance across key basal...
Abstract While CNS microglia have well-established roles in synapse pruning during neurodevelopment, only a few studies identified for formation. These focused on the cortex and primary sensory circuits restricted developmental time periods, leaving substantial gaps our understanding of early functions microglia. Here we investigated how absence impacts synaptic development nucleus accumbens (NAc), region critical emotional regulation motivated behaviors where dysfunction is implicated...
<title>Abstract</title> While CNS microglia have well-established roles in synapse pruning during neurodevelopment, only a few studies identified for formation. These focused on the cortex and primary sensory circuits restricted developmental time periods, leaving substantial gaps our understanding of early functions microglia. Here we investigated how absence impacts synaptic development nucleus accumbens (NAc), region critical emotional regulation motivated behaviors where dysfunction is...
Abstract Microglia play critical roles during CNS development and undergo dramatic changes in tissue distribution, morphology, gene expression as they transition from embryonic to neonatal adult microglial phenotypes. Despite the magnitude of these phenotypic shifts, little is known about time course dynamics transitions whether vary across brain regions. Here, we define maturation key regions basal ganglia mice, where significant regional differences phenotype are present adults. We found...
ABSTRACT Regeneration of propagating action potentials at nodes Ranvier allows nerve impulses to be conducted over long distances. Proper nodal function is believed rely on intimate associations among axons, myelinating oligodendrocytes, and perinodal astrocytes. Studies in the optic nerve, corpus callosum, spinal cord suggest that NG2 + cells are also key constituents CNS these glia may influence conduction efficacy formation axon collaterals. However, prevalence cell processes has not been...
Microglia have been found to acquire unique region-dependent deleterious features with age and diseases that contribute neuronal dysfunction degeneration in the brain. However, it remains unknown whether microglia exhibit similar phenotypic heterogeneity spinal cord. Here, we performed a regional analysis of cord 3-, 16-, 23-, 30-month-old mice. Using light electron microscopy, discovered an increasingly activated phenotype during course aging regardless location. causes ventral but not...
Abstract Vascular dementia (VaD) is a white matter ischemic disease and the second-leading cause of dementia, with no direct therapy. Within lesion site, cell-cell interactions dictate trajectory towards progression or repair. To elucidate underlying intercellular signaling pathways, VaD mouse model was developed for transcriptomic functional studies. The transcriptome integrated human snRNA-Seq dataset. A custom-made database encompassing 4053 2032 ligand-receptor (L-R) identified...
ABSTRACT Microglial capacity to adapt local tissue needs is a hallmark feature of these cells. Yet, full understanding the intracellular machinery that allows them rapidly adjust their cellular phenotype lacking. New studies show macrophage ability alter critically regulated by mitochondria. Indeed, mitochondria are increasingly recognized as key signaling and regulatory hubs, in addition well-established role ATP producers. Surprisingly little known about microglial vivo whether they play...
Platelets induce endothelial cell apoptosis via TGFβ1. We hypothesized that platelets are capable of inducing in sepsis up-regulation other platelet death mediators. BALB/c mice were bled 0 and 24h after cecal-ligation puncture. All developed signs sepsis. PLT cDNA microarrays showed 13 mediators (GO:0008219), particularly a 10-fold pro-apoptotic, Granzyme (Gzm) B (p=0.06), validated by RT-PCR [24h:0h relative expression (mean±SE) = 10.12±0.07, p=0.04]. This correlated well with...
ABSTRACT During aging, microglia produce inflammatory factors, show reduced tissue surveillance, altered interactions with synapses, and prolonged responses to insults, positioning these cells have profound impact on the functional integrity of nearby neurons. We others recently showed that microglial attributes differ significantly across brain regions CNS insults in young adult mice. However, degree which properties vary during aging is largely unexplored. Here, we analyze manipulate...
Highlighted Research Paper: AMPA Receptors Exist in Tunable Mobile and Immobile Synaptic Fractions In Vivo, by Haiwen Chen, Richard H. Roth, Elena Lopez-Ortega, Han L. Tan, Huganir.