Signaling pathways modulated by monocular enucleation in the superior colliculus of juvenile rats

Male 0301 basic medicine Superior Colliculi Glycogen Synthase Kinase 3 beta Neuronal Plasticity Eye Enucleation Rats 03 medical and health sciences Animals Female Phosphorylation Proto-Oncogene Proteins c-akt Signal Transduction
DOI: 10.1002/jdn.10095 Publication Date: 2021-02-06T10:08:20Z
ABSTRACT
AbstractMonocular eye enucleation (ME) is a classical paradigm to induce neural plasticity in retinal ganglion cells (RGCs) axons from the intact eye, especially when performed within the critical period of visual system development. However, the precise mechanisms underlying the axonal sprouting and synaptogenesis seen in this model remain poorly understood. In the present work, we investigated the temporal alterations in phosphorylation of three kinases related to axonal growth and synaptogenesis—GSK3β (an important repressor of axonal outgrowth), AKT, and ERK—in superior colliculus of rats submitted to ME during early postnatal development. Western blotting analysis showed an increase in pGSK3β, the inactive form of this enzyme, 24 and 48 hr after ME. Accordingly, an increase in pERK levels was detected 24 hr after ME, indicating that phosphorylation of these enzymes might be related to axonal reorganization induced by ME. Interestingly, AKT phosphorylation was increased just 1 week after ME, suggesting it may be involved in the stabilization of newly formed synapses, rising from the axonal reorganization of remaining eye. A better understanding of how signaling pathways are modulated in a model of intense axonal sprouting can highlight possible therapeutic targets in RGCs injuries in adult individuals, where axonal regrowth is nearly absent.
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