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Neuronal activity is a critical regulator of development and plasticity. Michelle Monje, professor of Neurology and Neurological Sciences at Stanford University and a Howard Hughes Medical Institute Investigator, presents on: Neuron-glial interactions in health and disease: from cognition to cancer, as part of the Distinguished Seminar Series by the Allen Institute.
Allen Institute, Seattle, WA
General public, Postdocs, Scientists
Talk Title: Neuron-glial interactions in health and disease: from cognition to cancer
Talk Abstract: In the central nervous system, neuronal activity is a critical regulator of development and plasticity. Activity-dependent proliferation of healthy glial progenitors, oligodendrocyte precursor cells (OPCs), and the consequent generation of new oligodendrocytes contributes to adaptive myelination. This plasticity of myelin tunes neural circuit function and contributes to healthy cognition, while disruption of myelin plasticity contributes to cancer therapy-related cognitive impairment. The robust mitogenic effect of neuronal activity on normal oligodendroglial precursor cells, a putative cellular origin for many forms of glioma, suggests that dysregulated or “hijacked” mechanisms of myelin plasticity might similarly promote malignant cell proliferation in this devastating group of brain cancers. Indeed, neuronal activity promotes progression of both high-grade and low-grade glioma subtypes in preclinical models. Crucial mechanisms mediating activity-regulated glioma growth include paracrine secretion of BDNF and the synaptic protein neuroligin-3 (NLGN3). NLGN3 induces multiple oncogenic signaling pathways in the cancer cell, and also promotes glutamatergic synapse formation between neurons and glioma cells. Glioma cells integrate into neural circuits synaptically through neuron-to-glioma synapses, and electrically through potassium-evoked currents that are amplified through gap-junctional coupling between tumor cells This synaptic and electrical integration of glioma into neural circuits is central to tumor progression in preclinical models. Thus, neuron-glial interactions not only modulate neural circuit structure and function in the healthy brain, but paracrine and synaptic neuron-glioma interactions also play important roles in the pathogenesis of glial cancers. The mechanistic parallels between normal and malignant neuron-glial interactions underscores the extent to which mechanisms of neurodevelopment and plasticity are subverted by malignant gliomas, and the importance of understanding the neuroscience of cancer.
The Distinguished Seminar Series features presentations by outstanding thinkers and scientists, sponsored by the Allen Institute for Brain Science and the Allen Institute for Neural Dynamics. Distinguished speakers are selected based on the impact of their interdisciplinary research to the neuroscience community. Speakers spend a full day visiting with research staff, are nominated by members of the Allen Institute, and selected by a committee of peers.
02.22.2024 | 10:30AM-11:30AM