Molas Casacuberta, Susanna, 1985-Gener, ThomasGüell, JofreMartín, MairenaBallesteros Yáñez, InmaculadaSanchez-Vives, Maria V.Dierssen, Mara2015-03-262015-03-262014Molas 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/s40478-014-0147-12051-5960http://hdl.handle.net/10230/23281Addiction 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.application/pdfeng© 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.Nicotina -- AddiccióHipocamp (Cervell)info:eu-repo/semantics/articlehttp://dx.doi.org/10.1186/s40478-014-0147-1CHRNA5/A3/B4CognitionHippocampusNeuroplasticityNeuroplasticityNicotineTobacco addictioninfo:eu-repo/semantics/openAccess