Our trainees review webinars in their given fields and share abstracts to help colleagues outside their discipline make an informed choice about watching them. As our program bridges diverse disciplines, these abstracts are beneficial for our own group in helping one another gain key knowledge in each other’s fields. We are happy to share these here for anyone else who may find them helpful.
Neuron-glial interactions in health and disease: from cognition to cancer
Michelle Monje, MD/PhD, Professor of Neurology at Stanford
November 5, 2020
Hosted by Pioneering Neurohealth: Stanford University
Analysis by Taylor Jorgensen:
In this seminar, Dr. Michelle Monje focuses on the intersection of translational medicine and basic science research that exists in glioma research. Gliomas are of particular interest to researchers as they are incredibly invasive and few current treatments lead to eradication of the malignancy.
Myelin dysregulation is one way by which gliomas arise in the brain, specifically through oligodendrocyte precursor cells (OPCs). Oligodendrocytes are responsible for providing myelin to neurons within the CNS. Changes in myelin plasticity have been shown in learning and cognition, as well as disease states like epilepsy. Some tumors resemble normal glial cells, so investigating normal gliogenesis may help to better understand tumor formation. In a healthy mouse brain, optogenetic stimulation of neurons increases the number of proliferating OPCs and changes the structure of myelin in the area, improving motor behavior. When human glioma tissue was grafted into mouse brains, stimulation of the glioma tissue resulted in increased tumor growth.
Dr. Monje’s research suggests that secreted factors may be responsible for activity-dependent OPC cell proliferation. Conditioned media was taken from cultured brain slices that were stimulated or inhibited and added to glioma cultures. The glioma cells showed state dependent proliferation that was enhanced by optogenetic stimulation and blocked by TTX. Two of the most likely mitogen factors are BDNF and NLGN3. The final portion of the seminar focuses on NLGN3, a post-synaptic adhesion molecule that is also found in oligodendrocytes. When NLGN3 is knocked out in the brain, tumor grafts do not expand and result in fewer structural synapses between the glioma and neurons.
Further research into oligodendrocyte and OPC function opens up the future treatment options for gliomas. Dr. Monje stresses the importance of integrating oncology and neuroscience, especially since gliomas are known to be electrically responsive tissues that are in network with neurons. I think this is an exciting prospect, as basic scientific research into other neurological pathologies could reveal novel uses for existing drugs and overlap into cancer research.