Decreased expression of synaptic genes in the vestibular ganglion of rodents following subchronic ototoxic stress.

Autor: Greguske EA; Departament de Ciències Fisiològiques, Universitat de Barcelona, Feixa Llarga s/n, 08907 l'Hospitalet de Llobregat, Catalunya, Spain; Institut de Neurociènces, Universitat de Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), 08907 l'Hospitalet de Llobregat, Catalunya, Spain., Maroto AF; Departament de Ciències Fisiològiques, Universitat de Barcelona, Feixa Llarga s/n, 08907 l'Hospitalet de Llobregat, Catalunya, Spain; Institut de Neurociènces, Universitat de Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), 08907 l'Hospitalet de Llobregat, Catalunya, Spain., Borrajo M; Departament de Ciències Fisiològiques, Universitat de Barcelona, Feixa Llarga s/n, 08907 l'Hospitalet de Llobregat, Catalunya, Spain; Institut de Neurociènces, Universitat de Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), 08907 l'Hospitalet de Llobregat, Catalunya, Spain. Electronic address: mborrajoarjona@ub.edu., Palou A; Departament de Ciències Fisiològiques, Universitat de Barcelona, Feixa Llarga s/n, 08907 l'Hospitalet de Llobregat, Catalunya, Spain; Institut de Neurociènces, Universitat de Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), 08907 l'Hospitalet de Llobregat, Catalunya, Spain. Electronic address: apaloumi45@ub.edu., Gut M; CNAG-CRG, Centre for Genomic Regulation, Barcelona Institute of Science and Technology (BIST), Barcelona, Spain; Universitat Pompeu Fabra, Barcelona, Spain. Electronic address: marta.gut@cnag.crg.eu., Esteve-Codina A; CNAG-CRG, Centre for Genomic Regulation, Barcelona Institute of Science and Technology (BIST), Barcelona, Spain; Universitat Pompeu Fabra, Barcelona, Spain. Electronic address: anna.esteve@cnag.crg.eu., Barrallo-Gimeno A; Departament de Ciències Fisiològiques, Universitat de Barcelona, Feixa Llarga s/n, 08907 l'Hospitalet de Llobregat, Catalunya, Spain; Institut de Neurociènces, Universitat de Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), 08907 l'Hospitalet de Llobregat, Catalunya, Spain. Electronic address: abarrallo@ub.edu., Llorens J; Departament de Ciències Fisiològiques, Universitat de Barcelona, Feixa Llarga s/n, 08907 l'Hospitalet de Llobregat, Catalunya, Spain; Institut de Neurociènces, Universitat de Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), 08907 l'Hospitalet de Llobregat, Catalunya, Spain. Electronic address: jllorens@ub.edu.
Jazyk: angličtina
Zdroj: Neurobiology of disease [Neurobiol Dis] 2023 Jun 15; Vol. 182, pp. 106134. Date of Electronic Publication: 2023 Apr 24.
DOI: 10.1016/j.nbd.2023.106134
Abstrakt: The vestibular ganglion contains primary sensory neurons that are postsynaptic to the transducing hair cells (HC) and project to the central nervous system. Understanding the response of these neurons to HC stress or loss is of great interest as their survival and functional competence will determine the functional outcome of any intervention aiming at repair or regeneration of the HCs. We have shown that subchronic exposure to the ototoxicant 3,3'-iminodipropionitrile (IDPN) in rats and mice causes a reversible detachment and synaptic uncoupling between the HCs and the ganglion neurons. Here, we used this paradigm to study the global changes in gene expression in vestibular ganglia using RNA-seq. Comparative gene ontology and pathway analyses of the data from both model species indicated a robust downregulation of terms related to synapses, including presynaptic and postsynaptic functions. Manual analyses of the most significantly downregulated transcripts identified genes with expressions related to neuronal activity, modulators of neuronal excitability, and transcription factors and receptors that promote neurite growth and differentiation. For choice selected genes, the mRNA expression results were replicated by qRT-PCR, validated spatially by RNA-scope, or were demonstrated to be associated with decreased expression of the corresponding protein. We conjectured that decreased synaptic input or trophic support on the ganglion neurons from the HC was triggering these expression changes. To support this hypothesis, we demonstrated decreased expression of BDNF mRNA in the vestibular epithelium after subchronic ototoxicity and also downregulated expression of similarly identified genes (e.g Etv5, Camk1g, Slc17a6, Nptx2, Spp1) after HC ablation with another ototoxic compound, allylnitrile. We conclude that vestibular ganglion neurons respond to decreased input from HCs by decreasing the strength of all their synaptic contacts, both as postsynaptic and presynaptic players.
Competing Interests: Declaration of Competing Interest The authors declare no competing interests.
(Copyright © 2023. Published by Elsevier Inc.)
Databáze: MEDLINE
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