Signaling Pathways and Cellular Mechanisms Regulating Mossy Fiber Sprouting in the Development of Epilepsy

Frontiers in Neurology
Christin M Godale, Steve C Danzer

Abstract

The sprouting of hippocampal dentate granule cell axons, termed mossy fibers, into the dentate inner molecular layer is one of the most consistent findings in tissue from patients with mesial temporal lobe epilepsy. Decades of research in animal models have revealed that mossy fiber sprouting creates de novo recurrent excitatory connections in the hippocampus, fueling speculation that the pathology may drive temporal lobe epileptogenesis. Conducting definitive experiments to test this hypothesis, however, has been challenging due to the difficulty of dissociating this sprouting from the many other changes occurring during epileptogenesis. The field has been largely driven, therefore, by correlative data. Recently, the development of powerful transgenic mouse technologies and the discovery of novel drug targets has provided new tools to assess the role of mossy fiber sprouting in epilepsy. We can now selectively manipulate hippocampal granule cells in rodent epilepsy models, providing new insights into the granule cell subpopulations that participate in mossy fiber sprouting. The cellular pathways regulating this sprouting are also coming to light, providing new targets for pharmacological intervention. Surprisingly, many invest...Continue Reading

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Citations

Sep 30, 2020·RNA Biology·Julie Qiaojin LinChristine E Holt
Mar 7, 2019·Epilepsy Currents·Steve C Danzer
Nov 25, 2019·Epilepsy & Behavior : E&B·Victor Rodrigues SantosOlagide Wagner de Castro
Oct 3, 2021·Proceedings of the National Academy of Sciences of the United States of America·Wenshu LuoCsaba Földy
Jul 3, 2021·Nature Communications·Murat KirtayZhao-Qi Wang

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