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dc.contributor.authorZiyatdinova, Sofya
dc.contributor.authorViswanathan, Jayashree
dc.contributor.authorHiltunen, Mikko
dc.contributor.authorTanila, Heikki
dc.contributor.authorPitkänen, Asla
dc.date.accessioned2016-07-19T10:07:53Z
dc.date.available2016-07-19T10:07:53Z
dc.date.issued2015-02-14
dc.identifierdoi: 10.1016/j.eplepsyres.2015.02.005
dc.identifier.citationReduction of epileptiform activity by valproic acid in a mouse model of Alzheimer's disease is not long-lasting after treatment discontinuation. Sofya Ziyatdinovaa, Jayashree Viswanathanb, Mikko Hiltunenb, Heikki Tanilaa, Asla Pitkänena. Doi:10.1016/j.eplepsyres.2015.02.005.fi_FI
dc.identifier.issn0920-1211
dc.identifier.urihttps://erepo.uef.fi/handle/123456789/117
dc.descriptionArticle
dc.description.abstractPatients with Alzheimer´s disease are at increased risk for unprovoked seizures and epilepsy compared with age-matched controls. Experimental evidence suggests that neuronal hyperexcitability and epilepsy can be triggered by amyloid-β (Aβ), the main component of amyloid plaques. Previous studies demonstrated that the administration of an anticonvulsant and histone deacetylase inhibitor, valproic acid, leads to a long-lasting reduction in Aβ levels. Here we used an APdE9 mouse model of Alzheimer's disease with overproduction of Aβ to assess whether treatment with valproic acid initiated immediately after epilepsy onset modifies the occurrence of epileptiform activity. We also analyzed whether the effect is long-lasting and associated with antiamyloidogenesis and histone-modifications. Male APdE9 mice (15 wk old) received daily intraperitoneal injections of 30 mg/kg valproic acid for 1 wk. After a 3-wk wash-out, the same animals received injections of a higher dose of valproic acid (300mg/kg) daily for 1 wk. Long-term video-electroencephalography monitoring was performed prior to, during, and after the treatments. Aβ and total histone H3 and H4 acetylation levels were measured at 1 month after the final valproic acid treatment. While 30 mg/kg valproic acid reduced spontaneous seizures in APdE9 mice (p<0.05, chi-square), epileptiform discharges were not reduced. Administration of 300 mg/kg valproic acid, however, reduced epileptiform discharges in APdE9 mice for at least 1 wk after treatment discontinuation (p<0.05, Wilcoxon test), but there was no consistent long-term effects on epileptiform activity after treatment withdrawal. Further, we found no longlasting effect on Aβ levels (p>0.05, Mann-Whitney test), only a meager increase in global acetylation of histone H3 (p<0.05), and no effects on H4 acetylation (p>0.05). In conclusion, valproic acid treatment of APdE9 mice at the stage when amyloid plaques are beginning to develop and epileptiform activity is detected reduced the amount of epileptiform activity, but the effect disappeared after treatment discontinuation.fi_FI
dc.language.isoenfi_FI
dc.publisherElsevier BVfi_FI
dc.relation.ispartofseriesEpilepsy Research
dc.relation.urihttp://dx.doi.org/10.1016/j.eplepsyres.2015.02.005
dc.rightsCC BY-NC-ND https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.titleReduction of epileptiform activity by valproic acid in a mouse model of Alzheimer's disease is not long-lasting after treatment discontinuationfi_FI
dc.typehttp://purl.org/eprint/type/JournalArticle
dc.description.versionFinal Draft
dc.contributor.departmentFaculty of Health Sciences
uef.solecris.id33278997
eprint.statushttp://purl.org/eprint/status/PeerReviewed
dc.type.publicationinfo:eu-repo/semantics/article
dc.rights.accessrights© Elsevier B.V
dc.relation.doi10.1016/j.eplepsyres.2015.02.005
dc.description.reviewstatushttp://purl.org/eprint/status/PeerReviewed
dc.relation.issn0920-1211
dc.relation.volume112
dc.rights.accesslevelopenAccess


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