Octadecylpropyl sulfamide reduces neurodegeneration and restores the memory deficits induced by hypoxia-ischemia in mice

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• dc.contributor.author Kossatz, Elkca
• dc.contributor.author Silva Peña, Danielca
• dc.contributor.author Suárez, Juanca
• dc.contributor.author de Fonseca, Fernando R.ca
• dc.contributor.author Maldonado, Rafael, 1961-ca
• dc.contributor.author Robledo, Patricia, 1958-ca
• dc.date.accessioned 2018-04-20T07:17:21Z
• dc.date.available 2018-04-20T07:17:21Z
• dc.date.issued 2018
• dc.description.abstract The PPAR-α agonist, oleoylethanolamide (OEA) has neuroprotective properties in stroke models. However, its rapid degradation represents a limitation for an effective therapeutic approach. In this study, we evaluated the effects of a stable OEA-modeled compound, octadecylpropyl sulfamide (SUL) on the cognitive, behavioral, cellular and molecular alterations associated with hypoxia-ischemia (HI) in mice. Mice subjected to HI were treated with the PPAR-α antagonist GW6471 (GW) (1 mg/kg) followed 15 min later by SUL (3 and 10 mg/kg). Behavioral, motor, and cognitive tests were carried out 24 h and 7 days after the HI. The levels of microglia, reactive astrocytes and neuronal nuclei were studied using immunofluorescence, and the expression of genes related to the N-acyl-ethanolamides/endocannabinoid signaling systems was determined by qRT-PCR at the end of the experimental sequence. HI induced brain damage in the ipsilateral hippocampus and cortex, which lead to severe memory impairments, and motor coordination deficits. Significant neuronal loss, increased microglia and reactive astrocytes, and compensatory changes in genes associated with the inflammation/immune and endocannabinoid systems were observed in these brain structures of lesioned mice. SUL reversed the memory and motor deficits, decreased the overexpression of microglia and astrocytes, and reduced neurodegeneration induced by HI. Cnr1 and Cnr2 gene expression was modulated by SUL in both sham and HI mice, while Pparα and Faah expression was regulated in HI mice. GW completely blocked the beneficial actions of SUL. These findings suggest that treatment with SUL reduces brain damage and the associated motor and memory deficits induced by HI probably by normalizing the changes in neuroinflammation/immune system mediators.
• dc.description.sponsorship This work was supported by Fundació La Marató de TV3 (#2011/111830) to RM and FF, AGAUR (#-ICREA Acadèmia-2015), AGAUR (#SGR2009-00731), and MINECO (#SAF2014-59648-P) to RM. Instituto de Salud Carlos III-RETICS/RTA (#RD16/0017) to RM and FF, and (PI16/01689) to FF. JS holds a “Miguel Servet II” research contract from ISCIII, FIMABIS and ERDF-EU (CPII17/00024).
• dc.format.mimetype application/pdf
• dc.identifier.citation Kossatz E, Silva-Peña D, Suárez J, de Fonseca FR, Maldonado R, Robledo P. Octadecylpropyl Sulfamide Reduces Neurodegeneration and Restores the Memory Deficits Induced by Hypoxia-Ischemia in Mice. Front. Pharmacol. 2018 Apr;9:376. DOI: 10.3389/fphar.2018.00376
• dc.identifier.doi http://dx.doi.org/10.3389/fphar.2018.00376
• dc.identifier.issn 1663-9812
• dc.identifier.uri http://hdl.handle.net/10230/34423
• dc.language.iso eng
• dc.publisher Frontiersca
• dc.relation.ispartof Frontiers in Pharmacology. 2018 Apr;9:376
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2014-59648-P
• dc.rights © 2018 Kossatz, Silva-Peña, Suárez, de Fonseca, Maldonado and Robledo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (http://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Hypoxia
• dc.subject.keyword Ischemia
• dc.subject.keyword Microglia
• dc.subject.keyword Memory deficits
• dc.subject.keyword Neurodegeneration
• dc.subject.keyword Neuroinflammatory
• dc.subject.keyword PPAR-α
• dc.subject.keyword Endocannabinoid
• dc.title Octadecylpropyl sulfamide reduces neurodegeneration and restores the memory deficits induced by hypoxia-ischemia in miceca
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion