Abstract:
:Neural stem cells are activated within neurogenic niches in response to brain injuries. This results in the production of neuroblasts, which unsuccessfully attempt to migrate toward the damaged tissue. Injuries constitute a gliogenic/non-neurogenic niche generated by the presence of anti-neurogenic signals, which impair neuronal differentiation and migration. Kinases of the protein kinase C (PKC) family mediate the release of growth factors that participate in different steps of the neurogenic process, particularly, novel PKC isozymes facilitate the release of the neurogenic growth factor neuregulin. We have demonstrated herein that a plant derived diterpene, (EOF2; CAS number 2230806-06-9), with the capacity to activate PKC facilitates the release of neuregulin 1, and promotes neuroblasts differentiation and survival in cultures of subventricular zone (SVZ) isolated cells in a novel PKC dependent manner. Local infusion of this compound in mechanical cortical injuries induces neuroblast enrichment within the perilesional area, and noninvasive intranasal administration of EOF2 promotes migration of neuroblasts from the SVZ towards the injury, allowing their survival and differentiation into mature neurons, being some of them cholinergic and GABAergic. Our results elucidate the mechanism of EOF2 promoting neurogenesis in injuries and highlight the role of novel PKC isozymes as targets in brain injury regeneration.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Domínguez-García S,Geribaldi-Doldán N,Gómez-Oliva R,Ruiz FA,Carrascal L,Bolívar J,Verástegui C,Garcia-Alloza M,Macías-Sánchez AJ,Hernández-Galán R,Nunez-Abades P,Castro Cdoi
10.1038/s41419-020-2453-9subject
Has Abstractpub_date
2020-04-22 00:00:00pages
262issue
4issn
2041-4889pii
10.1038/s41419-020-2453-9journal_volume
11pub_type
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