A5017962710- Neuroscience and Neuropharmacology Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurogenesis and neuroplasticity mechanisms
- Retinal Development and Disorders
- Neurobiology and Insect Physiology Research
- Neural dynamics and brain function
- Zebrafish Biomedical Research Applications
- RNA regulation and disease
- Mitochondrial Function and Pathology
- Axon Guidance and Neuronal Signaling
- CRISPR and Genetic Engineering
- Hepatitis B Virus Studies
- Cellular transport and secretion
- Barrier Structure and Function Studies
- Pain Mechanisms and Treatments
- Antibiotic Resistance in Bacteria
- Pancreatic function and diabetes
- Genetic Neurodegenerative Diseases
- Leptospirosis research and findings
- Photoreceptor and optogenetics research
- Virus-based gene therapy research
- Receptor Mechanisms and Signaling
- Memory and Neural Mechanisms
- Hepatitis C virus research
- Lipid Membrane Structure and Behavior
Duke Medical Center
2016-2025
Duke University
2016-2025
Duke University Hospital
2016-2025
Howard Hughes Medical Institute
2022-2025
Research Network (United States)
2023-2024
Aligning Science Across Parkinson's
2024
Duke Institute for Health Innovation
2014-2022
Institute of Neurobiology
2015-2022
Institute of Cell Biology
2015-2018
Allen Institute for Brain Science
2014-2018
Astrocytes regulate synaptic connectivity in the CNS through secreted signals. Here we identified two astrocyte-secreted proteins, hevin and SPARC, as regulators of excitatory synaptogenesis vitro vivo. Hevin induces formation synapses between cultured rat retinal ganglion cells. SPARC is not synaptogenic, but specifically antagonizes synaptogenic function hevin. are expressed by astrocytes superior colliculus, target cells, concurrent with synaptogenesis. Hevin-null mice had fewer synapses;...
Dendritic spines are the primary recipients of excitatory synaptic input in brain. Spine morphology provides important information on functional state ongoing transmission. One most commonly used methods to visualize is Golgi-Cox staining, which appealing both due ease sample preparation and wide applicability multiple species including humans. However, classification a time-consuming often expensive task that yields widely varying results between individuals. Here, we present novel approach...
One of the most important goals in neuroscience is to understand molecular cues that instruct early stages synapse formation. As such it has become imperative develop objective approaches quantify changes synaptic connectivity. Starting from sample fixation, this protocol details how number both dissociated neuronal culture and brain sections using immunocytochemistry. Using compartment-specific antibodies, we label presynaptic terminals as well sites postsynaptic specialization. We define...
Astrocytes strongly promote the formation and maturation of synapses by secreted proteins. Several astrocyte-secreted synaptogenic proteins controlling excitatory synapse development were identified; however, those that induce inhibitory synaptogenesis remain elusive. Here, we identify neurocan as an protein. After secretion from astrocytes, is cleaved into N- C-terminal fragments. We found these fragments have distinct localizations in extracellular matrix. The fragment localizes to...
Thrombospondins 1 and 2 (TSP-1/2) belong to a family of extracellular glycoproteins with angiostatic synaptogenic properties. Although TSP-1/2 have been postulated drive the resolution postischemic angiogenesis, their role in synaptic functional recovery is unknown. We investigated whether are necessary for motor after stroke. Focal ischemia was induced 8- 12-week-old wild-type (WT) knockout (KO) mice by unilateral occlusion distal middle cerebral artery common carotid (CCA). increased...
During cortical synaptic development, thalamic axons must establish connections despite the presence of more abundant intracortical projections. How thalamocortical synapses are formed and maintained in this competitive environment is unknown. Here, we show that astrocyte-secreted protein hevin required for normal connectivity mouse cortex. Absence results a profound, long-lasting reduction accompanied by transient increase excitatory connections. Three-dimensional reconstructions neurons...
Abstract Huntington’s Disease (HD) is a neurodegenerative disease caused by poly-glutamine expansion in the Htt protein, resulting misfolding and cell death. Expression of cellular protein folding pro-survival machinery heat shock transcription factor 1 (HSF1) ameliorates biochemical neurobiological defects misfolding. We report that HSF1 degraded cells mice expressing mutant Htt, medium spiny neurons derived from human HD iPSCs brain samples patients with HD. Mutant increases CK2α′ kinase...
Astrocytes control excitatory synaptogenesis by secreting thrombospondins (TSPs), which function via their neuronal receptor, the calcium channel subunit α2δ-1. α2δ-1 is a drug target for epilepsy and neuropathic pain; thus TSP–α2δ-1 interaction implicated in both synaptic development disease pathogenesis. However, mechanism this promotes requirement connectivity of developing mammalian brain are unknown. In study, we show that global or cell-specific loss yields profound deficits synapse...
Huntington9s disease (HD) is a neurodegenerative caused by the expansion of poly-glutamine (poly-Q) stretch in huntingtin (Htt) protein. Gain-of-function effects mutant Htt have been extensively investigated as major driver neurodegeneration HD. However, loss-of-function poly-Q mutations recently emerged potential drivers pathophysiology. Early synaptic problems excitatory cortical and striatal connections reported HD, but role protein connectivity was unknown. Therefore, we <i>in vivo</i>...
Neuropathic pain is a common cause of after nerve injury, but its molecular basis poorly understood. In post-gene chip microarray effort to identify new target genes contributing neuropathic development, we report here the characterization novel contributor, thrombospondin-4 (TSP4), using model spinal ligation injury. TSP4 mainly expressed in astrocytes and significantly upregulated injury side dorsal cord that correlates with development states. blockade by intrathecal antibodies, antisense...