Neurofilaments and Neurofilament Proteins in Health and Disease

Nonuniform distribution of neurofilaments (NFs) along axons. (A–C) Electron micrographs of mouse optic axons magnified equally and viewed at three levels—50 µm (A), 2000 µm (B), and 7000 µm (C) from the eye—and summarized in cartoon form above. In these axons, NFs are sixfold more numerous distally than proximally. (D) Electron micrograph of a node of Ranvier in the long section showing the node of Ranvier flanked by internodal segments insulated by layers of compact myelin (My). (Adapted from Porter and Bonneville 1973.) Enlarged images of myelinated (1 and 4) and unmyelinated regions (2 and 3) are displayed in insets (D1–D4). (E) An electron micrograph of a different node of Ranvier in the long section showing how the myelin sheath terminates through widening rims of myelin loops and the ensheathed axon becomes naked in the region of the node of Ranvier (adapted, with permission, from Spacek 2004 ). Insets (E1 and E2) are enlarged images of myelinated (1) and unmyelinated (2) regions. The cytoskeleton organization of unmyelinated portions of the optic axons and node of Ranvier is strikingly different from that of the myelinated portions just a short distance away, reflecting the influence of oligodendroglial or Schwann cell signaling on NF organization. RE, retinal excavation. Scale bars, 200 nm (A,B,C); 300 nm (D); 100 nm (D1–D4); 600 nm (E); 100 nm (E1–E2).