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Alterations in the Serotonin and Dopamine Pathways by Cystathionine Beta Synthase Overexpression in Murine Brain

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Abstract

Cystathionine beta synthase (CBS) is one of the 225 genes on chromosome 21 (HSA 21) that are triplicated in persons with trisomy 21 (Down syndrome). Although most triplicate HSA21 genes have their orthologous genes on murine chromosome 16, the murine ortholog of hCBS is on murine chromosome 17 and thus is not present in the well-studied Ts65Dn mouse model of trisomy 21. Persons with trisomy 21 (T21) present deficits in neurotransmission and exhibit early brain aging that can partially be explained by monoamine neurotransmitter alterations. We used transgenic mice for the hCBS gene, which overexpress the CBS protein in various brain regions, to study if CBS overexpression induces modifications in the monoamine neurotransmitters in the hypothalamus, thalamus, hippocampus, and striatum from transgenic and control female and male mice aged 3–4 months and 11–12 months. Sex, age, and brain area each influenced neurotransmitter levels. Briefly, the serotonin pathway was modified by CBS overexpression in various brain areas in female mice but not in male mice. The dopamine pathway was modified in brain regions according to sex and age. These results may allow us to better understand the role of the transsulfuration pathway and especially CBS overexpression in the metabolism of biogenic amines and the catecholamine catabolism in persons with trisomy 21.

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Acknowledgements

We thank the personnel of the animal facility of the University Paris-Diderot for taking care of the animals for health and control. We thank for funding CNRS, the European Commission (AnEUploidy project LSHG-CT-2006-037627) and the AFRT (Association Française pour la Recherche sur la Trisomie 21) for grants (2013-2015) and financial support for NFK.

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  1. Unité de Biologie Fonctionnelle et Adaptative (BFA), Université Paris Diderot, Sorbonne Paris Cité, CNRS UMR 8251, 75205, Paris, France

    J. London, F. K. Ndiaye, L. C. Bui, B. Souchet, F. Daubigney, C. Magnan, S. Luquet, J. Dairou, N. Janel & C. Rouch

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  1. J. London
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Contributions

DJ, LJ, and RC designed the study; BLC, NDK, and RC performed the HPLC experiments; DF, LJ, RC, and SB performed the other experiments; LJ, NDK, and RC analyzed the data; LJ and RC wrote the paper. JN, LS, and MC corrected the manuscript.

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Correspondence to J. London.

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This study was approved by the Animal Ethical Committee of University Paris Diderot (CEEA-40, approval number CEB-001-2011).

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The authors declare that they have no conflict of interest.

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London, J., Ndiaye, F.K., Bui, L.C. et al. Alterations in the Serotonin and Dopamine Pathways by Cystathionine Beta Synthase Overexpression in Murine Brain. Mol Neurobiol 56, 3958–3971 (2019). https://doi.org/10.1007/s12035-018-1323-2

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