A5069709350- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neuropharmacology Research
- Immune Response and Inflammation
- Neurogenesis and neuroplasticity mechanisms
- Tryptophan and brain disorders
- Stress Responses and Cortisol
- Axon Guidance and Neuronal Signaling
- Nerve injury and regeneration
- Genetics and Neurodevelopmental Disorders
- Virus-based gene therapy research
- RNA Interference and Gene Delivery
- Autism Spectrum Disorder Research
- Glycosylation and Glycoproteins Research
- interferon and immune responses
- Neuroscience and Neural Engineering
- Ion channel regulation and function
- Retinal Development and Disorders
- Protein Tyrosine Phosphatases
- Photoreceptor and optogenetics research
- Child Development and Digital Technology
- Barrier Structure and Function Studies
- Viral Infections and Immunology Research
- Immunotherapy and Immune Responses
- Complement system in diseases
- T-cell and B-cell Immunology
Princeton University
2009-2025
University of California, San Diego
1999-2016
Harvard University
2000-2004
Boston University
2004
Wesleyan University
1995
Class I major histocompatibility complex (class MHC) molecules, known to be important for immune responses antigen, are expressed also by neurons that undergo activity-dependent, long-term structural and synaptic modifications. Here, we show in mice genetically deficient cell surface class MHC or a receptor component, CD3ζ, refinement of connections between retina central targets during development is incomplete. In the hippocampus adult mutants, N -methyl- d -aspartate receptor–dependent...
Regional variations in the expression of a striatal enriched protein tyrosine phosphatase called STEP were studied adult rat brain by combination immunocytochemistry, lesion studies, Western blotting, and situ hybridization. Monoclonal antibodies generated against identified multiple polypeptides M(r) 46, 37, 33 doublet 64-66 kDa on blots. Although three immunoreactive bands with lower molecular weights cytosolic fractions, was membrane fractions. All forms abundant caudate-putamen present...
Recombinant adeno-associated viruses (AAVs) allow rapid and efficient gene delivery to the nervous system, are widely used in neuroscience research, basis of FDA-approved neuron-targeting therapies. Here we find that an innate immune response AAV genome reduces dendritic length complexity disrupts synaptic transmission mouse somatosensory cortex. Dendritic loss is apparent 3 weeks after injection experimentally relevant viral titers, not restricted a particular capsid serotype, transgene,...
Neurotrophins have been implicated in activity-dependent synaptic plasticity, but the underlying intracellular mechanisms remain largely unknown. Synaptic potentiation induced by brain-derived neurotrophic factor (BDNF), not neurotrophin 3, was prevented blockers of adenosine 3',5'-monophosphate (cAMP) signaling. Activators cAMP signaling alone were ineffective modifying efficacy greatly enhanced effect BDNF. Blocking abolished facilitation BDNF-induced presynaptic activity. Thus actions...
Proteins of the major histocompatibility complex class I (MHCI) are known for their role in immunity and have recently been implicated long-term plasticity excitatory synaptic transmission. However, mechanisms by which MHCI influences remain unknown. Here we show that endogenous regulates responses mediated NMDA-type glutamate receptors (NMDARs) mammalian central nervous system (CNS). The AMPA/NMDA ratio is decreased at MHCI-deficient hippocampal synapses, reflecting an increase...
Proteins of the major histocompatibility complex class I (MHCI) negatively regulate synapse density in developing vertebrate brain (Glynn et al., 2011; Elmer 2013; Lee 2014), but underlying mechanisms remain largely unknown. Here we identify a novel MHCI signaling pathway that involves inhibition known synapse-promoting factor, insulin receptor. Dominant-negative receptor constructs decrease Xenopus visual system (Chiu 2008), and activation increases dendritic spine mouse hippocampal neurons...
Memory impairment is a common feature of conditions that involve changes in inflammatory signaling the brain, including traumatic brain injury, infection, neurodegenerative disorders, and normal aging. However, causal importance mediators cognitive impairments these remains unclear. Here we show specific immune proteins, members major histocompatibility complex class I (MHC I), are essential for hippocampus-dependent memory, specifically required NMDAR-dependent forms long-term depression...
Abstract An increasing number of studies support an unexpected role for immune molecules in regulating healthy brain functions during development and adulthood. Here we review the roles specific (including cytokines, components complement cascade, members major histocompatibility complex class I family their receptors) formation plasticity glutamatergic synapses. These findings add a new dimension to our understanding neural–immune interactions, suggest novel molecular mechanisms that may...
Members of the major histocompatibility complex (MHC) class I family proteins are well known for their central role in adaptive immune system, where they present self and non-self peptides surveillance. Although brain has been long considered privileged, part because an apparent lack neuronal MHC I, it since shown that expressed by normal, uninfected neurons. Moreover, expression is unusually dynamic developing adult brain, levels neurons can be regulated endogenous exogenous electrical...
Recombinant adeno-associated viruses (AAVs) allow rapid and efficient gene delivery in the nervous system. AAVs are widely used research basis of multiple FDA-approved therapies. Here, we find that immune response to AAV’s genome reduces dendritic complexity mammalian cortex. Dendritic loss associated with AAV-mediated occurs at experimentally-relevant titers, cannot be explained by responses transgene expression or surgery, is not restricted a particular capsid serotype, encoded transgene,...
Major histocompatibility complex class I (MHCI) proteins present antigenic peptides for immune surveillance and play critical roles in nervous system development plasticity. Most MHCI are transmembrane proteins. The extracellular domain of interacts with immunoreceptors, peptides, co-receptors to mediate signaling. While the cytoplasmic also plays important endocytic trafficking, cross-presentation extracellularly derived antigens, CTL priming, molecular mediators signaling by remain largely...