Human polymorphisms in nicotinic receptors: a functional analysis in iPS-derived dopaminergic neurons.
- Authors
- Deflorio, Cristina; Blanchard, Stéphane; Carisì, Maria Carla; Bohl, Delphine; Maskos, Uwe
- Year
- 2017
- Journal
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology
- PMID
- 27856558
- DOI
- 10.1096/fj.201600932R
Tobacco smoking is a public health problem, with ∼5 million deaths per year, representing a heavy burden for many countries. No effective therapeutic strategies are currently available for nicotine addiction, and it is therefore crucial to understand the etiological and pathophysiological factors contributing to this addiction. The neuronal α5 nicotinic acetylcholine receptor (nAChR) subunit is critically involved in nicotine dependence. In particular, the human polymorphism α5D398N corresponds to the strongest correlation with nicotine dependence risk found to date in occidental populations, according to meta-analysis of genome-wide association studies. To understand the specific contribution of this subunit in the context of nicotine addiction, an efficient screening system for native human nAChRs is needed. We have differentiated human induced pluripotent stem (iPS) cells into midbrain dopaminergic (DA) neurons and obtained a comprehensive characterization of these neurons by quantitative RT-PCR. The functional properties of nAChRs expressed in these human DA neurons, with or without the polymorphism in the α5 subunit, were studied with the patch-clamp electrophysiological technique. Our results in human DA neurons carrying the polymorphism in the α5 subunit showed an increase in EC, indicating that, in the presence of the polymorphism, more nicotine or acetylcholine chloride is necessary to obtain the same effect. This human cell culturing system can now be used in drug discovery approaches to screen for compounds that interact specifically with human native and polymorphic nAChRs.-Deflorio, C., Blanchard, S., Carisì, M. C., Bohl, D., Maskos, U. Human polymorphisms in nicotinic receptors: a functional analysis in iPS-derived dopaminergic neurons.
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| Progression of differentiation of iPSCs into specific subtypes of neurons. | Wang J et al. | — | 2025 | → |
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| Genetic susceptibility to nicotine addiction: Advances and shortcomings in our understanding of the CHRNA5/A3/B4 gene cluster contribution. | Icick R et al. | — | 2020 | → |
| Negative Symptoms of Schizophrenia and Dopaminergic Transmission: Translational Models and Perspectives Opened by iPSC Techniques. | Collo G et al. | — | 2020 | → |
| Neural circuits and nicotinic acetylcholine receptors mediate the cholinergic regulation of midbrain dopaminergic neurons and nicotine dependence. | Xiao C et al. | — | 2020 | → |
| The nicotinic receptor alpha5 coding polymorphism rs16969968 as a major target in disease: Functional dissection and remaining challenges. | Maskos U | — | 2020 | → |
| The α5 Nicotinic Acetylcholine Receptor Subunit Differentially Modulates α4β2<sup>*</sup> and α3β4<sup>*</sup> Receptors. | Scholze P et al. | — | 2020 | → |
| Translational Molecular Approaches in Substance Abuse Research. | Fulton SL et al. | — | 2020 | → |
| Profound alteration in reward processing due to a human polymorphism in CHRNA5: a role in alcohol dependence and feeding behavior. | Besson M et al. | — | 2019 | → |
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| The role of the nAChR subunits α5, β2, and β4 on synaptic transmission in the mouse superior cervical ganglion. | Simeone X et al. | — | 2019 | → |
| A Human Polymorphism in CHRNA5 Is Linked to Relapse to Nicotine Seeking in Transgenic Rats. | Forget B et al. | — | 2018 | → |
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