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2014-11-11

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cc-by (c) Molas, Susanna et al., 2014
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/106546

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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https://doi.org/10.1186/s40478-014-0147-1

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 α5, α3 and β4 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.

Subject

Cognició, Hipocamp (Cervell), Neuroplasticitat, Nicotina

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Cognition, Hippocampus (Brain), Neuroplasticity, Nicotine

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Articles publicats en revistes (Cognició, Desenvolupament i Psicologia de l'Educació)

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MOLAS, Susanna, et al. 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. Vol. 2, num. 1, pags. 147. ISSN 2051-5960. [consulted: 9 of June of 2026]. Available at: https://hdl.handle.net/2445/106546

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