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A multi-omic study for uncovering molecular mechanisms associated with hyperammonemia-induced cerebellar function impairment in rats

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A multi-omic study for uncovering molecular mechanisms associated with hyperammonemia-induced cerebellar function impairment in rats

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dc.contributor.author Tarazona, Sonia es_ES
dc.contributor.author Carmona, Héctor es_ES
dc.contributor.author Conesa, Ana es_ES
dc.contributor.author Llansola, Marta es_ES
dc.contributor.author Felipo, Vicente es_ES
dc.date.accessioned 2023-09-21T18:04:37Z
dc.date.available 2023-09-21T18:04:37Z
dc.date.issued 2021-02 es_ES
dc.identifier.issn 0742-2091 es_ES
dc.identifier.uri http://hdl.handle.net/10251/196895
dc.description.abstract [EN] Patients with liver cirrhosis may develop covert or minimal hepatic encephalopathy (MHE). Hyperammonemia (HA) and peripheral inflammation play synergistic roles in inducing the cognitive and motor alterations in MHE. The cerebellum is one of the main cerebral regions affected in MHE. Rats with chronic HA show some motor and cognitive alterations reproducing neurological impairment in cirrhotic patients with MHE. Neuroinflammation and altered neurotransmission and signal transduction in the cerebellum from hyperammonemic (HA) rats are associated with motor and cognitive dysfunction, but underlying mechanisms are not completely known. The aim of this work was to use a multi-omic approach to study molecular alterations in the cerebellum from hyperammonemic rats to uncover new molecular mechanisms associated with hyperammonemia-induced cerebellar function impairment. We analyzed metabolomic, transcriptomic, and proteomic data from the same cerebellums from control and HA rats and performed a multi-omic integrative analysis of signaling pathway enrichment with the PaintOmics tool. The histaminergic system, corticotropin-releasing hormone, cyclic GMP-protein kinase G pathway, and intercellular communication in the cerebellar immune system were some of the most relevant enriched pathways in HA rats. In summary, this is a good approach to find altered pathways, which helps to describe the molecular mechanisms involved in the alteration of brain function in rats with chronic HA and to propose possible therapeutic targets to improve MHE symptoms. es_ES
dc.description.sponsorship This work was supported by the Ministerio de Ciencia e Innovación of Spain (SAF2017-82917-R) and Consellería Educación Generalitat Valenciana (PROMETEOII/2014/033), co-funded with European Regional Development Funds (ERDF). es_ES
dc.language Inglés es_ES
dc.publisher Springer-Verlag es_ES
dc.relation.ispartof Cell Biology and Toxicology es_ES
dc.rights Reserva de todos los derechos es_ES
dc.subject Hyperammonemia es_ES
dc.subject Multi-omics es_ES
dc.subject Cerebellum es_ES
dc.subject Signaling pathways es_ES
dc.subject Neurotransmission es_ES
dc.subject Immune system es_ES
dc.subject.classification ESTADISTICA E INVESTIGACION OPERATIVA es_ES
dc.title A multi-omic study for uncovering molecular mechanisms associated with hyperammonemia-induced cerebellar function impairment in rats es_ES
dc.type Artículo es_ES
dc.identifier.doi 10.1007/s10565-020-09572-y es_ES
dc.relation.projectID info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2017-82917-R/ES/BASES MOLECULARES DE LAS ALTERACIONES NEUROLOGICAS (COGNITIVAS Y MOTORAS) EN HIPERAMONEMIA Y ENCEFALOPATIA HEPATICA. LMPLICACIONES TERAPEUTICAS/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/GVA//PROMETEOII%2F2014%2F033/ es_ES
dc.rights.accessRights Abierto es_ES
dc.contributor.affiliation Universitat Politècnica de València. Escola Tècnica Superior d'Enginyeria Informàtica es_ES
dc.description.bibliographicCitation Tarazona, S.; Carmona, H.; Conesa, A.; Llansola, M.; Felipo, V. (2021). A multi-omic study for uncovering molecular mechanisms associated with hyperammonemia-induced cerebellar function impairment in rats. Cell Biology and Toxicology. 37(1):129-149. https://doi.org/10.1007/s10565-020-09572-y es_ES
dc.description.accrualMethod S es_ES
dc.relation.publisherversion https://doi.org/10.1007/s10565-020-09572-y es_ES
dc.description.upvformatpinicio 129 es_ES
dc.description.upvformatpfin 149 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion es_ES
dc.description.volume 37 es_ES
dc.description.issue 1 es_ES
dc.identifier.pmid 33404927 es_ES
dc.relation.pasarela S\425433 es_ES
dc.contributor.funder Generalitat Valenciana es_ES
dc.contributor.funder Agencia Estatal de Investigación es_ES
dc.contributor.funder European Regional Development Fund es_ES
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