Figure 3. 12-month of age motor cortex of Hdh^d•hyp mice exhibit neuronal loss and myelination abnormalities.

a-b depicts Nissl stained cross-sections of 12-month of age motor cortices. Compared to CTL (n = 5), Hdh^d•hyp (n = 8) cortical thickness (μm; c) and numbers of neurons (d) of layer VI are reduced, whereas the numbers of degenerating cells is increased (n_{per genotype} = 3; e). Representative TEM micrographs of normal and degenerating neurons from 12-month of age CTL and Hdh^d•hyp are shown in f and g, respectively. h-j shows Hdh^d•hyp neurons containing intracytoplasmic zebra-bodies (h-i arrowheads). k depicts Hdh^d•hyp axonal processes displaying Wallerian-like degenerative morphology. l-m corresponds to TEM micrographs showing layer VI myelinated axonal processes. *asterisk in m points to under-myelinated axons. Arrowhead and arrow in m point to a myelin ballon and tubulovesicular structures, respectively. n depicts g-ratios of myelinated axons. Compared with CTL, the periodicity of myelin lamellae of large axons located in Hdh^d•hyp cortical layer VI is reduced (n = 37 axons [pool of 3 biological replicas per genotype]; o). Error bars in c-e and o represent ±SEM. Scale bars in b, f-g, h, i and j-m correspond to 150, 0.75, 4, 1 and 0.5 μm, respectively.