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. 2021 Mar 12;13:645334. doi: 10.3389/fnagi.2021.645334

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Copyright © 2021 Miguel, Perez, Malek-Ahmadi and Mufson.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Photomicrographs showing Calr-ir cells (A,C,E) and beaded climbing fibers (B,D,F) in the GL and ML, respectively, in a 66-year-old female HC (A,B), 46-year-old male with DSD+ (C,D), and a 72-year-old female with AD (E,F) case. Note the reduction of Calr-ir cells in DS (C) and AD (E) compared to HC (A). High-power images of an elongated Lugaro (G) shown in (A) (upper arrow) and a unipolar brush cell (H) (lower arrow in A) from a HC, Golgi cell (J) shown in (C) (arrow) and a unipolar brush interneuron in DS (I), as well unipolar brush cells (K: indicated by an arrow in E; and L) in an AD case. Note the presence of GL Calr-ir MF rosettes in (G–I) (arrows). Boxplots showing a significant reduction in Calr-ir cell numbers in DS compared to HC (M; Kruskal–Wallis, p < 0.001) and AD (M; Kruskal–Wallis, p < 0.002), even after adjusting for age and gender (N; ANCOVA, p > 0.005). The number of Calr-ir Golgi, unipolar brush, and Lugaro cells was significantly reduced in DS compared to HC (O; Golgi and brush: Kruskal–Wallis, p < 0.01; Lugaro: Krukal–Wallis, p < 0.001) and AD (O; Golgi and brush: Kruskal–Wallis, p < 0.01; Lugaro: Kruskal–Wallis, p < 0.001). Age and gender adjustment revealed a significant reduction in the Golgi, brush, and Lugaro Calr-ir cell number in DS compared to HC, and only Golgi Calr-ir cell numbers were also reduced compared to AD (P). CF, climbing fibers; MF, mossy fibers. Asterisks in (B,D,F) indicate PCs. Scale bars: (E) = 50 μm applies to (A,C), (F) = 25 μm applies to (B,D), and (L) = 10 μm applies to (G–K). * denotes significance between groups.