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bioRxiv · 10.1101/062679

Cell fusion proteins can rejuvenate adult dendritic trees

Veronika Kravtsov·Meital Oren-Suissa·Benjamin Podbilewicz
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Abstract

The aging brain undergoes structural changes, affecting brain homeostasis, neuronal function and consequently cognition. The complex architecture of dendritic arbors poses a challenge to understanding age-dependent morphological alterations, behavioral plasticity and remodeling following brain injury. Here, we use the PVD polymodal neurons of C. elegans as a model to study how aging affects neuronal plasticity. Using confocal live imaging of C. elegans PVD neurons, we demonstrate age-related progressive morphological alterations of intricate dendritic arbors. We show that insulin/IGF-1 receptor mutations (daf-2) fail to inhibit the progressive morphological aging of dendrites and do not prevent the minor decline in response to harsh touch during aging. We uncovered that PVD aging is characterized by a major decline in regenerative potential of dendrites following experimental laser dendrotomy. Furthermore, the remodeling of transected dendritic trees via AFF-1-mediated self-fusion can be restored in old animals by DAF-2 insulin/IGF-1 receptor mutations, and can be differentially reestablished by ectopic expression of AFF-1 fusion protein (fusogen). Thus, AFF-1 fusogen ectopically expressed in the PVD and mutations in DAF-2/IGF-1R, differentially rejuvenate some aspects of dendritic regeneration following injury.\n\nSummary statementEctopic expression of AFF-1 fusogen or low activity of IGF-1R/DAF-2 rejuvenate the regeneration potential of dendrites following injury in aging C. elegans

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Veronika Kravtsov, Meital Oren-Suissa, Benjamin Podbilewicz. 2016-07-07. Cell fusion proteins can rejuvenate adult dendritic trees. https://doi.org/10.1101/062679

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