Fig. 3.

Examination of human C9orf72 post-mortem spinal cord tissue shows reduced expression of complexes I and IV of the mitochondrial electron transport chain in ventral horn motor, but not dorsal horn sensory, neurons. a Representative photomicrographs showing reduced expression of MT-ND2 (complex I) and MT-CO3 (complex IV) transcripts in ventral horn motor neurons of the post-mortem spinal cord from a C9orf72 hexanucleotide repeat expansion mutation case compared with its age- and sex-matched control. Red spots highlight individual mRNA molecules of MT-ND2 or MT-CO3. Tissue was counterstained with haematoxylin. Scale bars = 50 µm. Orange asterisk denotes an anterior horn motor neuron. Bar chart depicts the quantification of the number of MT-ND2 and MT-CO3 transcripts per ventral horn spinal motor neuron. Bars represent aggregate mean ± SEM, with each dot representing the mean count for between one and five cells for each of the five post-mortem specimens for C9orf72-ALS (red bars) and their age- and sex-matched controls (blue bars). Statistical significance was evaluated with the Kruskal–Wallis test with FDR correction. b Representative photomicrographs of the dorsal horn sensory neurons, examined using the same probes that recognise individual mRNA of MT-ND2 or MT-CO3, showing comparable expression between the same cases and controls. Scale bars = 50 µm. Orange asterisk denotes a dorsal horn sensory neuron. Bar chart depicts the quantification of the number of MT-ND2 and MT-CO3 transcripts per dorsal horn neuron. Bars represent aggregate mean ± SEM, with each dot representing the mean count for between one and five cells for each of the five post-mortem specimens for C9orf72-ALS (red bars) and their age- and sex-matched controls (blue bars). Statistical significance was evaluated with the Kruskal–Wallis test with FDR correction for multiple comparisons. *p < 0.05, **p < 0.01, ‘ns’ denotes non-significant result (p ≥ 0.05)