Article
Effects of classical PKC activation on hippocampal neurogenesis and cognitive performance: mechanism of action
Author/s | Domínguez García, Samuel
Gómez Oliva, Ricardo Geribaldi Doldán, Noelia Hierro Bujalance, Carmen Sendra, Marta Ruiz, Félix A. Carrascal Moreno, María Livia Núñez Abades, Pedro Antonio Castro, Carmen |
Department | Universidad de Sevilla. Departamento de Fisiología |
Publication Date | 2021 |
Deposit Date | 2022-04-19 |
Published in |
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Abstract | 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 ... 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 PKCα activation and promotes transforming growth factor alpha (TGFα) 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. |
Funding agencies | Ministerio de Ciencia, Innovación y Universidades (MICINN). España European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER) Junta de Andalucía Universidad de Cádiz |
Project ID. | RTI-2018-099908-B-C21
RTI-2018-099908-B-C22 MICINN/FEDER BFU2016-75038R FEDER-UCA18-106647 |
Citation | Domínguez García, S., Gómez Oliva, R., Geribaldi Doldán, N., Hierro Bujalance, C., Sendra, M., Ruiz, F.A.,...,Castro, C. (2021). Effects of classical PKC activation on hippocampal neurogenesis and cognitive performance: mechanism of action. Neuropsychopharmacology, 46 (6), 1207-1219. |
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