RT journal article
T1 Effects of classical PKC activation on hippocampal neurogenesis and cognitive performance: mechanism of action
A1 Domínguez García, Samuel
A1 Gómez Oliva, Ricardo
A1 Geribaldi Doldán, Noelia
A1 Hierro Bujalance, Carmen
A1 Sendra, Marta
A1 Ruiz Rodríguez, Félix Alejandro
A1 Carrascal, Livia
A1 Macías Sánchez, Antonio José
A1 Verástegui Escolano, Cristina
A1 Hernández Galán, Rosario
A1 García Alloza, Mónica
A1 Nunez Abades, Pedro
A1 Castro González, Carmen
A2 Anatomía y Embriología Humana
A2 BiomedicinaBiotecnología y Salud Pública
A2 Química Orgánica
AB Hippocampal neurogenesis has widely been linked to memory and learning performance. New neurons generated from neural stem cells (NSC) within the dentate gyrus of the hippocampus (DG) integrate in hippocampal circuitry participating in memory tasks. Several neurological and neuropsychiatric disorders show cognitive impairment together with a reduction in DG neurogenesis. Growth factors secreted within the DG promote neurogenesis. Protein kinases of the protein kinase C (PKC) family facilitate the release of several of these growth factors, highlighting the role of PKC isozymes as key target molecules for the development of drugs that induce hippocampal neurogenesis. PKC activating diterpenes have been shown to facilitate NSC proliferation in neurogenic niches when injected intracerebroventricularly. We show in here that long-term administration of diterpene ER272 promotes neurogenesis in the subventricular zone and in the DG of mice, affecting neuroblasts differentiation and neuronal maturation. A concomitant improvement in learning and spatial memory tasks performance can be observed. Insights into the mechanism of action reveal that this compound facilitates classical PKC alpha activation and promotes transforming growth factor alpha (TGF alpha) and, to a lesser extent, neuregulin release. Our results highlight the role of this molecule in the development of pharmacological drugs to treat neurological and neuropsychiatric disorders associated with memory loss and a deficient neurogenesis.
PB SPRINGERNATURE
SN 0893-133X
YR 2020
FD 2020-12
LK http://hdl.handle.net/10498/24312
UL http://hdl.handle.net/10498/24312
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 06-nov-2026