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. 2020 Jun 22;10:10035. doi: 10.1038/s41598-019-57236-7

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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NAD⁺ and OT levels were determined in the cortex and hypothalamus or cerebrospinal fluid (CSF) of wild-type (BL6) and CD157KO mice treated with NR. (a,b) NR gavage at 3 mg/mouse for 12 days significantly elevated NAD⁺ concentrations in mice of both genotypes in the cortex (two-way ANOVA; the effect of treatment (F_1,27 = 28.33, P < 0.0001) and the effect of genotype (F_1,27 = 4.74, P = 0.0384) and the hypothalamus (two-way ANOVA; the effect of treatment (F_1,42 = 36.58, P < 0.0001). Bonferroni’s post hoc comparison shows a significant difference between placebo and NR in CD157KO mice (P < 0.05)), comparing saline treatment (PL). (c) The identical treatment of NR significantly increased OT concentrations in the CSF of CD157KO mice (Two-way ANOVA revealed a significant effect of interaction between treatment and genotypes (F_1,60 = 7.341, P = 0.0088). Bonferroni’s post hoc comparison shows a significant difference between placebo and NR in CD157KO mice (P < 0.05). (d) OT concentrations in the hypothalamus in wild-type and CD157KO mice showed no significant difference after treatment with NR (Two-way ANOVA showed the only effect of genotype (F_1,36 = 12.59, P = 0.0011). *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001, respectively.