Hippocampal changes produced by overexpression of the human CHRNA5/A3/B4 gene cluster may underlie cognitive deficits rescued by nicotine in transgenic mice

Molas Casacuberta, Susanna, 1985-; Gener, Thomas; Güell, Jofre; Martín, Mairena; Ballesteros Yáñez, Inmaculada; Sanchez-Vives, Maria V.; Dierssen, Mara

Hippocampal changes produced by overexpression of the human CHRNA5/A3/B4 gene cluster may underlie cognitive deficits rescued by nicotine in transgenic mice

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dc.contributor.author Molas Casacuberta, Susanna, 1985-ca
dc.contributor.author Gener, Thomasca
dc.contributor.author Güell, Jofreca
dc.contributor.author Martín, Mairenaca
dc.contributor.author Ballesteros Yáñez, Inmaculadaca
dc.contributor.author Sanchez-Vives, Maria V.ca
dc.contributor.author Dierssen, Maraca
dc.date.accessioned 2015-03-26T08:27:05Z
dc.date.available 2015-03-26T08:27:05Z
dc.date.issued 2014ca
dc.description.abstract Addiction involves long-lasting maladaptive changes including development of disruptive drug-stimuli associations. Nicotine-induced neuroplasticity underlies the development of tobacco addiction but also, in regions such as the hippocampus, the ability of this drug to enhance cognitive capabilities. Here, we propose that the genetic locus of susceptibility to nicotine addiction, the CHRNA5/A3/B4 gene cluster, encoding the ?5, ?3 and ?4 subunits of the nicotinic acetylcholine receptors (nAChRs), may influence nicotine-induced neuroadaptations. We have used transgenic mice overexpressing the human cluster (TgCHRNA5/A3/B4) to investigate hippocampal structure and function in genetically susceptible individuals. TgCHRNA5/A3/B4 mice presented a marked reduction in the dendrite complexity of CA1 hippocampal pyramidal neurons along with an increased dendritic spine density. In addition, TgCHRNA5/A3/B4 exhibited increased VGLUT1/VGAT ratio in the CA1 region, suggesting an excitatory/inhibitory imbalance. These hippocampal alterations were accompanied by a significant impairment in short-term novelty recognition memory. Interestingly, chronic infusion of nicotine (3.25 mg/kg/d for 7 d) was able to rescue the reduced dendritic complexity, the excitatory/inhibitory imbalance and the cognitive impairment in TgCHRNA5/A3/B4. Our results suggest that chronic nicotine treatment may represent a compensatory strategy in individuals with altered expression of the CHRNA5/A3/B4 region.en
dc.description.sponsorship The laboratory of Mara Dierssen is supported by Departament d'Universitats, Recerca i Societat de la Informació (Grups consolidats 09 2009SGR1313). This work was supported by Grants SAF2010-16427, SAF2007-31093-E, and FIS (PI 082038); Marató TV3; the Jerome Lejeune, Koplowitz, FRAXA and Areces Foundations; and the European Union (CureFXS ERare-EU/FIS PS09102673, EU- Era NET Neuron. FOOD for THOUGHT F4T). The laboratory of Mairena Martín is supported by Ministerio de Economía y Competitividad (BFU2011-23034). The Centro de Investigación Biomédica en Red de Enfermedades Raras is an initiative of the Instituto de Salud Carlos III. The laboratory of María V. Sánchez is supported by Ministerio de Economía y Competitividad (BFU2011-27094)en
dc.format.mimetype application/pdfca
dc.identifier.citation Molas S, Gener T, Güell J, Martín M, Ballesteros-Yáñez I, Sanchez-Vives MV, Dierssen M. Hippocampal changes produced by overexpression of the human CHRNA5/A3/B4 gene cluster may underlie cognitive deficits rescued by nicotine in transgenic mice. Acta Neuropathologica Communications. 2014; 2(1): 147. DOI 10.1186/s40478-014-0147-1ca
dc.identifier.doi http://dx.doi.org/10.1186/s40478-014-0147-1
dc.identifier.issn 2051-5960ca
dc.identifier.uri http://hdl.handle.net/10230/23281
dc.language.iso engca
dc.publisher BioMed Centralca
dc.relation.ispartof Acta Neuropathologica Communications. 2014; 2(1): 147
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SGR2009-1313
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2010-16427
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PN/SAF2007-31093
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2011-23034
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2011-27094
dc.rights © 2014 Molas et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.ca
dc.rights.accessRights info:eu-repo/semantics/openAccessca
dc.rights.uri http://creativecommons.org/licenses/by/4.0
dc.subject.keyword CHRNA5/A3/B4en
dc.subject.keyword Cognitionen
dc.subject.keyword Hippocampusen
dc.subject.keyword Neuroplasticityen
dc.subject.keyword Neuroplasticityen
dc.subject.keyword Nicotineen
dc.subject.keyword Tobacco addictionen
dc.subject.other Nicotina -- Addiccióca
dc.subject.other Hipocamp (Cervell)ca
dc.title Hippocampal changes produced by overexpression of the human CHRNA5/A3/B4 gene cluster may underlie cognitive deficits rescued by nicotine in transgenic miceen
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/publishedVersionca

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