Letrozole Potentiates Mitochondrial and Dendritic Spine Impairments Induced by β Amyloid

Figure 5

Letrozole and 𝐴𝛽_1--42 reduce synaptic proteins. (a) Representative 3D reconstructions of dendritic segments from sister cultures that were treated with either control, 𝐴𝛽_1--42 (1 μM), and letrozole (1 μm) or 𝐴𝛽_1--42 + letrozole (1 μm) for 24 or 72 hours and immunostained for synaptophysin (white) and synaptopodin (red). Scale bar, 2 μm. (b) Quantification of the densities of synaptopodin-positive puncta following treatments. There is a significant decrease in synaptopodin puncta after 24 and 72 hours of 𝐴𝛽_1--42, letrozole or 𝐴𝛽_1--42 + letrozole treatments compared to control conditions. After 72 hours, the number of synaptopodin puncta was significantly lower in letrozole and 𝐴𝛽_1--42 + letrozole-treated cultures compared to 𝐴𝛽_1--42 alone. When synaptopodin puncta densities were compared between 24- and 72-hour treated cultures there was a significant decrease only in letrozole and 𝐴𝛽_1--42 + letrozole-treated cultures after 72 hours. 24 hours: control, n = total dendritic segment lengths of 1041 μm from 12 cells in 4 cultures; 𝐴𝛽_1--42, 𝑛=633 μm of dendrite from 8 cells in 4 cultures; letrozole, 𝑛=952 μm of dendrite from 10 cells in 4 cultures; 𝐴𝛽_1--42 + letrozole, 𝑛=1007 μm of dendrite from 10 cells in 4 cultures. 72 hours: control, 𝑛 = total dendritic segment lengths of 559 μm from 10 cells in 3 cultures; 𝐴𝛽_1--42, 𝑛=472 μm of dendrite from 9 cells in 4 cultures; letrozole, 𝑛=838 μm of dendrite from 9 cells in 4 cultures; 𝐴𝛽_1--42 + letrozole, 𝑛=750 μm of dendrite from 8 cells in 4 cultures. There is a significant decrease in synaptophysin puncta after 24 and 72 hours of 𝐴𝛽_1--42, letrozole, or 𝐴𝛽_1--42 + letrozole treatments compared to control conditions. After 72 hours, the number of synaptophysin puncta was significantly lower in letrozole and 𝐴𝛽_1--42 + letrozole-treated cultures compared to 𝐴𝛽_1--42 alone When synaptophysin puncta densities were compared between 24- and 72-hour treated cultures there was a significant decrease in 𝐴𝛽_1--42, letrozole, and 𝐴𝛽_1--42 + letrozole-treated cultures after 72 hours. 24 hours: control, n = total dendritic segment lengths of 1041 μm from 12 cells in 4 cultures; 𝐴𝛽_1--42, 𝑛=633 μm of dendrite from 8 cells in 4 cultures; letrozole, 𝑛=952 μm of dendrite from 10 cells in 4 cultures; 𝐴𝛽_1--42 + letrozole, 𝑛=1007 μm of dendrite from 10 cells in 4 cultures. 72 hours: control, n = total dendritic segment lengths of 559 μm from 10 cells in 3 cultures; 𝐴𝛽_1--42, 𝑛=472 μm of dendrite from 9 cells in 4 cultures; letrozole, 𝑛=838 μm of dendrite from 9 cells in 4 cultures; 𝐴𝛽_1--42 + letrozole, 𝑛=750 μm of dendrite from 8 cells in 4 cultures.

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