HDAC4N increases with Braak stage in CA2 hippocampal pyramidal cells.

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HDAC4N increases with Braak stage in CA2 hippocampal pyramidal cells. HDAC4N increases with Braak stage in CA2 hippocampal pyramidal cells. A, B, Representative paraffin sections double labeled with ATM 2C1 (brown) and HDAC4 (blue). Signals of ATM 2C1 were strong in neurons of NL (A) but not of AD (B) frontal cortex. HDAC4 was found predominantly in cytoplasm in NL brains, but took up a nuclear location in AD brains in neurons with weak ATM 2C1 signal. Scale bar, 20 μm. C–H, Paraffin sections of human hippocampus were immunostained with HDAC4 (brown) and counterstained with hematoxylin (blue/purple). C, E, G, Low-magnification images showing the frequency of HDAC4 in the CA2 subfield (marked by rectangles). Scale bar, 200 μm. D, F, H, Higher-magnification images showing cells with the HDAC4N phenotype (arrows). Scale bar, 50 μm. Different Braak stages are represented. C and D are from NL case patients (Braak stages 0-2); E and F are from M subjects (Braak stages 3-4); and G and H are from AD subjects (Braak stages 5-6). Insets in the top right corner of D, F, and H offer enlargements of representative neurons showing the different phenotypes. Green arrows, HDAC4C; red arrows, HDAC4N. G, HDAC4N percentage in CA2 neurons as a function of Braak stages. Difference determined by unpaired t test: *p < 0.05; **p < 0.01; ***p < 0.001 (n = 8-9). H, HDAC4N percentage as a function of CDR scores. CDR0, n = 9; CDR1, n = 3; CDR2 to 3, n = 10. Difference determined by unpaired t test, ns > 0.05; ***p < 0.001. Xuting Shen et al. eneuro 2016;3:ENEURO.0124-15.2016 ©2016 by Society for Neuroscience