Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 605, Issue -, Pages 141-147Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2022.03.071
Keywords
CRMP2; Mossy fiber sprouting; Epilepsy
Categories
Funding
- National Natural Science Foundation of China [81771308, 31771184, 31970901]
- Shanghai Pujiang Program [19PJ1402200]
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Mossy fiber sprouting is a characteristic of epilepsy and plays a key role in neural circuit formation. CRMP2, whose phosphorylation state regulates neurite/axon outgrowth, has been reported to change in epilepsy patients and animal models. This study provides direct evidence supporting the role of CRMP2 in mossy fiber sprouting in an animal model of epilepsy.
As a hallmark of epilepsy, mossy fiber sprouting was regarded as an ideal mode to study neural rewiring upon injury. The process of mossy fiber sprouting constitutes key steps for neural circuit formation, including axon collateral formation and outgrowth, reversed pathfinding and synapse connection. The canonical function of CRMP2 is to promote neurite/axon outgrowth via binding to tubulin heterodimers, which is mainly regulated by its phosphorylation state. CRMP2 expression and phosphorylation were reported to change in medial temporal epilepsy patients and animal modes of epilepsy. As a novel anti-epilepsy drug, Lacosamide is able to impair CRMP2 mediated tubulin polymerization. Previous studies suggested possible roles of CRMP2 in mossy fiber sprouting. Here, we provide direct evidence to support the role of CRMP2 in the process of mossy fiber sprouting in an animal model of epilepsy. We found that CRMP2 phosphorylation was downregulated specifically in the hippocampus during latent phase of epileptic rats. In addition, with the reduction of CRMP2 expression levels in dentate gyrus by CRMP2 shRNA, we observed decreased mossy fiber sprouting in these CRMP2 knockdown rats. Our results demonstrated that CRMP2 modulates mossy fiber sprouting in dentate gyrus of pilocarpine induced rat model of epilepsy.(c) 2022 Elsevier Inc. All rights reserved.
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