Research Paper Volume 10, Issue 11 pp 3507—3527

Angiopoietin-1 and ανβ3 integrin peptide promote the therapeutic effects of L-serine in an amyotrophic lateral sclerosis/Parkinsonism dementia complex model

Figure 12. Representative electron micrographs showing mitochondrial atrophy, fragmented vacuoles, loose and fused alterations of the myelin sheath, and apoptotic features of the nuclei of spinal cord anterior horn motor neurons in the vehicle-treated model rats, as well as the attenuating effects of treatment with C16+Ang-1, L-serine, or both. (AB) Rats in the control group showed (A) normal neuronal nuclei with uncondensed chromatin and (B) normal myelinated axons with dark, ring-shaped myelin sheaths surrounding the axons, with normal shaped mitochondria. (C-D, K-L, S-T) In vehicle-treated model rats 2–8 weeks after L-BMAA injection, fragmented vacuoles and loose and fused alterations on the myelin sheath were found, as well as mitochondrial malformations such as vacuolization and swollen cristae (arrows in D). At 8 weeks after L-BMAA injection (T), some mitochondria had a completely atrophied appearance, and their cristae had vanished. More drastic alterations in demyelination and axonal loss were found (L, T), and neurons also showed apoptotic features with a contracted nucleus and condensed, fragmented, and marginated nuclear chromatin (C, K, S). By contrast, in rats treated with C16+Ang-1(E-F, M-N, U-V), L-serine (G-H, O-P, W-X), and both (I-J, Q-R, Y-Z), newly formed myelin sheaths were observed surrounding the intact axons, and the morphology of mitochondria and nuclei were relatively normal. This was particularly obvious in the group that received the combined treatment (Y, Z). (B, H, T, V) Scale bar = 500 nm; (D, J, L, P, R, Z) scale bar = 1 μm; (C, E, F, K, N, S, U, W, X, Y) scale bar = 2 μm; (A, G, I, M, O, Q) scale bar = 5 μm.