Figure 6. OSCP overexpression ameliorates Aβ-induced mitochondrial dysfunction in mouse neurons.

Mouse cortical neurons were exposed to 500 nM oligomeric Aβ1–42 for 24 h. (a) Attenuated oligomeric Aβ1–42-induced OSCP reduction by OSCP overexpression. Western blot images show OSCP expression level in mouse primary neurons which is representative of seven samples in each group. (b) Shows immunofluorescent staining of OSCP (green) in primary cultured neurons. COXIV (red) was used to determine the localization of OSCP in mitochondria. *P<0.01 versus other groups. Scale bar, 20 μm. (c) OSCP overexpression protected mitochondrial membrane potential against oligomeric Aβ1–42 toxicity. The upper panel of representative images shows the TMRM staining and the lower panel shows phase contrast images. Scale bar, 20 μm. *P<0.01 versus other groups. n=40–64 neurons from at least three independent experiments. (d) OSCP overexpression protected neuron ATP reduction against oligomeric Aβ1–42 toxicity. *P<0.01 versus other groups. n=12 samples of each group from at least three independent experiments. (e) Attenuated Aβ-induced reduction in neuritic mitochondrial population by OSCP overexpression. *P<0.01 versus other groups. n=22–27 neurons from at least three independent experiments. The upper panel of representative images shows the merged staining of MAP2 (green, dendrite) and Mito-Dsred (red, mitochondria). Scale bar, 20 μm. The middle panel shows Mito-Dsred staining and the lowest panel shows enlarged images from the indicated areas. (f) Ameliorated Aβ-sensitized mPTP formation by OSCP overexpression. Ionophore (2 μM) was used to trigger mPTP formation. *P<0.05 versus vehicle-treated control and OSCP OE neurons. ^#P<0.05 versus Aβ-treated OSCP OE neurons. n=4–6 independent experiment. Control refers to neurons infected with control lentivirus carrying backbone vector. OSCP OE refers to neurons infected with lentivirus carrying OSCP cDNA. Error bars represent s.e.m.