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. 2019 Mar 27;9:5273. doi: 10.1038/s41598-019-41654-8

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© The Author(s) 2019

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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Drug dose-effect responses and systemic effects. (A–C) Area of ChAT immunoreactive cells in animals given LM11A-31 once daily for three months from age 15 to 18 months, at the indicated doses (n = 7–9 each). Values in a matched young cohort (age 4 months, n = 8) are indicated by the dashed line. Treatment inhibited the age-associated decrease in cholinergic neuron area in total (MS + VDB) and similarly in the MS and VDB individually. Composite data for all cholinergic cells (MS + VDB) yielded an EC₅₀ of 11.77 mg/kg. (D) Mean body weights in each group as a proportion of pretreatment weights (31.4–33.0 g) did not change significantly over the course of the experiment. (E) Three-month treatment with LM11A-31 at 5–50 mg/kg had no effect on brain weights at 18 months. Values are expressed as mean + sem.