Professor Beth Stevens (Harvard University Program in Immunology)Nov 2016 Simon Foundation Lecture On New Science of Microglia Function in the Healthy Developing and Mature Brain and the Implications for Autism and Schizophrenia |
Stevens discusses her Harvard lab's work uncovering the molecular biology behind the critical role microglia play in the developing healthy brain -- as phagocytic sculpters/refiners/architects of the brain's vast and initially unruly synaptic network.
She discusses how dysregulation of the microglial process of synaptic refinement during development may be at the root of a diverse set of complicated neuro-developmental disorders,including autism and schizophrenia. Further, she discusses how this large scale synapto-phagocytic machinery -- turned off for most part after development -- can be aberrantly turned back on in the mature brain leading to network damaging synapse loss, Evidence now suggests that region specific microglial driven synapse loss precedes disease manifestation in the major neuro-degenerative diseases, including Huntington's and Alzheimers, and therefore may be a root cause of diverse neuro-degenerative disease |
Stevens, Beth, Role of Microglia in Synaptic Pruning in Normal Brain Development and in Neuro-developmental and Neuro-degenerative Disorder and DiseaseStevens, Beth, Role of Microglia in Synaptic Pruning in Normal Brain Development and in Neuro-developmental and Neuro-degenerative Disorner and Disease |
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Barres, Ben 2017, Role of Microglia activated A1 Phenotype Astrocytes in Neurodegenerative Diseases Ranging from AD to ALS, MS, and retinal degeneration - 2017 Broad Institute Lecture, MIT |
A totally remarkable presentation of recent work by the Barres Lab at Stanford University which has illuminated the neurodegenerative and destructive role of A1 activated astrocytes. Barres lab has shown that A1 activation is driven by immunologically reactive microglia, and, in particular, the production exclusively by microglia of the IL-1alpha, TNF-alpha, and C1q cytokines in response to immune challenge (such as LPS) or injury (such as ischemic stroke). These signalling molecules then trigger a robust functional change in astrocytes from a neurotrophic functional profile to a neurotoxic, and neuro-phagocytic functional profile.
Importantly, Barres and colleagues showed that the immune challenge itself was insufficient to trigger A1 activation of astrocytes. . The presence of microglia, and, more specifically, the presence of microglial derived inflammatory cytokines was required for the damaging transformation of astrocytes to an A1 neurotoxic profile. |
Wake et al, 2009,
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Microglial Process making Contact with and Altering Post-synaptic Spine Along Single Dendrite
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Microglia Process Making Contact with and Altering Pre-synaptic Bouton along Single Axon
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