Methylphenidate attenuates the cognitive and mood alterations observed in mbnl2 knockout mice and reduces mcroglia overexpression

Ramon-Duaso, Carla; Gener, Thomas; Consegal, Marta; Fernández-Avilés, Cristina; Gallego, Juan José; Castarlenas, Laura; Swanson, Maurice S.; Torre Fornell, Rafael de la; Maldonado, Rafael, 1961-; Puig Velasco, María Victoria; Robledo, Patricia, 1958-

Methylphenidate attenuates the cognitive and mood alterations observed in mbnl2 knockout mice and reduces mcroglia overexpression

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dc.contributor.author Ramon-Duaso, Carlaca
dc.contributor.author Gener, Thomasca
dc.contributor.author Consegal, Martaca
dc.contributor.author Fernández-Avilés, Cristinaca
dc.contributor.author Gallego, Juan Joséca
dc.contributor.author Castarlenas, Lauraca
dc.contributor.author Swanson, Maurice S.ca
dc.contributor.author Torre Fornell, Rafael de laca
dc.contributor.author Maldonado, Rafael, 1961-ca
dc.contributor.author Puig Velasco, María Victoriaca
dc.contributor.author Robledo, Patricia, 1958-ca
dc.date.accessioned 2018-09-12T07:32:09Z
dc.date.issued 2019
dc.description.abstract Myotonic dystrophy type 1 (DM1) is a multisystem disorder affecting muscle and central nervous system (CNS) function. The cellular mechanisms underlying CNS alterations are poorly understood and no useful treatments exist for the neuropsychological deficits observed in DM1 patients. We investigated the progression of behavioral deficits present in male and female muscleblind-like 2 (Mbnl2) knockout (KO) mice, a rodent model of CNS alterations in DM1, and determined the biochemical and electrophysiological correlates in medial prefrontal cortex (mPFC), striatum and hippocampus (HPC). Male KO exhibited more cognitive impairment and depressive-like behavior than female KO mice. In the mPFC, KO mice showed an overexpression of proinflammatory microglia, increased transcriptional levels of Dat, Drd1, and Drd2, exacerbated dopamine levels, and abnormal neural spiking and oscillatory activities in the mPFC and HPC. Chronic treatment with methylphenidate (MPH) (1 and 3 mg/kg) reversed the behavioral deficits, reduced proinflammatory microglia in the mPFC, normalized prefrontal Dat and Drd2 gene expression, and increased Bdnf and Nrf2 mRNA levels. These findings unravel the mechanisms underlying the beneficial effects of MPH on cognitive deficits and depressive-like behaviors observed in Mbnl2 KO mice, and suggest that MPH could be a potential candidate to treat the CNS deficiencies in DM1 patients.
dc.description.sponsorship Fundació la Marató de TV3 (231/C/2014), and Instituto de Salud Carlos III (PI14/00210) to P.R.; Agency for Management of University and Research Grants (AGAUR) (ICREA Acadèmia-2015), AGAUR (SGR2009-00731), Ministerio de Economía Industria y Competitividad (MINECO) (SAF2014-59648-P), and Instituto de Salud Carlos III-RETICS/RTA (RD16/0017/0020) to R.M.; MINECO (SAF2016-80726-R) to M.V.P.; and AGAUR (SGR2014-680) to R.T.F.
dc.format.mimetype application/pdf
dc.identifier.citation Ramon-Duaso C, Gener T, Consegal M, Fernández-Avilés C, Gallego JJ, Castarlenas L et al. Methylphenidate attenuates the cognitive and mood alterations observed in mbnl2 knockout mice and reduces mcroglia overexpression. Cereb Cortex. 2019;29(7):2978-97. DOI: 10.1093/cercor/bhy164
dc.identifier.doi http://dx.doi.org/10.1093/cercor/bhy164
dc.identifier.issn 1047-3211
dc.identifier.uri http://hdl.handle.net/10230/35437
dc.language.iso eng
dc.publisher Oxford University Pressca
dc.relation.ispartof Cerebral Cortex. 2019;29(7):2978-97
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2014-59648-P
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-80726-R
dc.rights © Oxford University Press. This is a pre-copyedited, author-produced version of an article accepted for publication in Cerebral Cortex following peer review. The version of record Ramon-Duaso C, Gener T, Consegal M, Fernández-Avilés C, Gallego JJ, Castarlenas L. Methylphenidate attenuates the cognitive and mood alterations observed in mbnl2 knockout mice and reduces mcroglia overexpression. Cereb Cortex. 2019; 29(7): 2978-2997 is available online at: http://doi.org/10.1093/cercor/bhy164
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.subject.other Miotonia atròfica
dc.subject.other Dopamina
dc.subject.other Metilfenidat
dc.subject.other Micròglia
dc.title Methylphenidate attenuates the cognitive and mood alterations observed in mbnl2 knockout mice and reduces mcroglia overexpressionca
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/acceptedVersion

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