The authors investigated the mechanisms of dysfunction of mitochondria that occur early in neurodegeneration, for example in Huntington’s disease and aging.
The spinal cords of live mice were imaged using a Bruker Ultima IV dual-channel two-photon microscope to detect mitochondria from the surface to a depth of 100 to 200 μm using Thy1-Mito-CFP transgenic mice, where all neuronal mitochondria have cyan fluorescent protein (CFP). A water-immersion 16× objective lens (0.8 N.A.; CFI785; Nikon Instruments) was used to acquire 1,024 × 1,024 pixels (407.5 × 407.5 µm) images over ∼4.8 s using Prairie View software. Stacks were continuously acquired along depth (z stacks) every 2 µm from 180 to 200 µm below the surface of the spinal cord.
Progressive distal mitochondrial protein damage was resolved along the spinal cords. Such damage causes impaired mitochondrial protein import in distal neuronal compartments. This fundamental physiologic mechanism, which controls neurite plasticity/vulnerability and is amplified during stress and neurodegeneration, is described as “neuritosis.” This is a neuronal regulatory mechanism that is likely important for neurodevelopment and is pathologically exacerbated during aging, stress, and neurodegenerative diseases.