Ribosomal S6 kinase signaling regulates neuronal viability during development and confers resistance to excitotoxic cell death in mature neurons.

Autor: Hoyt KR; Division of Pharmaceutics and Pharmacology, Ohio State University, Columbus, OH, USA. Electronic address: hoyt.31@osu.edu., Horning P; Department of Neuroscience, Ohio State University, Columbus, OH, USA; Division of Pharmaceutics and Pharmacology, Ohio State University, Columbus, OH, USA., Georgette Ang P; Division of Pharmaceutics and Pharmacology, Ohio State University, Columbus, OH, USA., Karelina K; Department of Neuroscience, Ohio State University, Columbus, OH, USA., Obrietan K; Department of Neuroscience, Ohio State University, Columbus, OH, USA. Electronic address: obrietan.1@osu.edu.
Jazyk: angličtina
Zdroj: Neuroscience [Neuroscience] 2024 Oct 18; Vol. 558, pp. 1-10. Date of Electronic Publication: 2024 Aug 11.
DOI: 10.1016/j.neuroscience.2024.08.012
Abstrakt: The Ribosomal S6 Kinase (RSK) family of serine/threonine kinases function as key downstream effectors of the MAPK signaling cascade. In the nervous system, RSK signaling plays crucial roles in neuronal development and contributes to activity-dependent neuronal plasticity. This study examined the role of RSK signaling in cell viability during neuronal development and in neuroprotection in the mature nervous system. Using neuronal cell-culture-based profiling, we found that suppressing RSK signaling led to significant cell death in developing primary neuronal cultures. To this end, treatment with the RSK inhibitors BiD1870 or SL0101 on the first day of culturing resulted in over 80% cell death. In contrast, more mature cultures showed attenuated cell death upon RSK inhibition. Inhibition of RSK signaling during early neuronal development also disrupted neurite outgrowth and cell growth. In maturing hippocampal explant cultures, treatment with BiD1870 had minimal effects on cell viability, but led to a striking augmentation of NMDA-induced cell death. Finally, we used the endothelin 1 (ET-1) model of ischemia to examine the neuroprotective effects of RSK signaling in the mature hippocampus in vivo. Notably, in the absence of RSK inhibition, the granule cell layer (GCL) was resistant to the effects of ET-1; However, disruption of RSK signaling (via the microinjection of BiD1870) prior to ET-1 injection triggered cell death within the GCL, thus indicating a neuroprotective role for RSK signaling in the mature nervous system. Together these data reveal distinct, developmentally-defined, roles for RSK signaling in the nervous system.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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