![FXR1 and FXR2 are altered in human lumbar spinal cord α-MNs of sALS and fALS patients. (A) FXR1and (B) FXR2 show moderate, predominantly Nissl substance-associated staining of normal control α-MNs. In sALS as well as in C9orf72- and FUS-linked fALS, FXR1 and FXR2 immunoreactivity of up to ∼40% of α-MNs is enhanced while labelling of ∼5–20% is reduced (white arrows). Note the more granular, speckled pattern of cytoplasmic FXR2 immunoreactivity that was often seen in sALS and fALS α-MNs with reduced FXR2 staining intensity. Focal, subplasmalemmal larger structures intensely labelled for FXR1 or FXR2, respectively, were prominent in α-MNs of sALS and fALS cases and possibly correspond to enlarged cisternae of the ER and/or accumulations/aggregates of FXR1 and FXR2 (black arrows; scale bars = 60 µm). (C) Quantification of aberrant expression (compared to the mean intensity of control staining) and accumulation of FXR1 and FXR2 in spinal cord α-MNs of controls and ALS cases studied [n = 6 controls, 4 FUSR521C, 4 C9orf72 and 6 sALS; 54 ± 24 (mean ± SD) motor neurons analysed each; bars indicate mean ± SEM; *P ≤ 0.05, **P ≤ 0.01, **P ≤ 0.001 in an unpaired, two-tailed Student’s t-test; asterisks represent P-values compared to the controls].](https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/brain/144/4/10.1093_brain_awab018/3/awab018f6.jpeg?Expires=1750727747&Signature=cGduA0-UDvgZDFrISErdeoTvy5xT-ImROM40wtI5UpasCM-EY0xMrLupMdpNf0gkcoc2DGgE1St9tr8j3jOLvyEd5~vexd0vAHHiYr~mVwAHDQom9mglqqan6tstwqlG3AExm7PRPTmdFEgANIoij7wb7BrX-WVvgU8ejg4f8UPq17h3XF-yjcsTh0Hg6xV5w-K4Bzy0VNkAiCg4mlV5zhVBhKJSteNUpuvHhfZALRaVb9ynsoZ04zlECadORYGBKdo~j0LpG7rLA02iUBLEipdkgHbazff4hanoyV4p82isW3OPYQYsCFOCm3~k5iUuROt-KnQyMmrsHtAqT9lcAQ__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
FXR1 and FXR2 are altered in human lumbar spinal cord α-MNs of sALS and fALS patients. (A) FXR1and (B) FXR2 show moderate, predominantly Nissl substance-associated staining of normal control α-MNs. In sALS as well as in C9orf72- and FUS-linked fALS, FXR1 and FXR2 immunoreactivity of up to ∼40% of α-MNs is enhanced while labelling of ∼5–20% is reduced (white arrows). Note the more granular, speckled pattern of cytoplasmic FXR2 immunoreactivity that was often seen in sALS and fALS α-MNs with reduced FXR2 staining intensity. Focal, subplasmalemmal larger structures intensely labelled for FXR1 or FXR2, respectively, were prominent in α-MNs of sALS and fALS cases and possibly correspond to enlarged cisternae of the ER and/or accumulations/aggregates of FXR1 and FXR2 (black arrows; scale bars = 60 µm). (C) Quantification of aberrant expression (compared to the mean intensity of control staining) and accumulation of FXR1 and FXR2 in spinal cord α-MNs of controls and ALS cases studied [n = 6 controls, 4 FUSR521C, 4 C9orf72 and 6 sALS; 54 ± 24 (mean ± SD) motor neurons analysed each; bars indicate mean ± SEM; *P ≤ 0.05, **P ≤ 0.01, **P ≤ 0.001 in an unpaired, two-tailed Student’s t-test; asterisks represent P-values compared to the controls].
