Figure 3.

Electron micrographs demonstrating microglial activation, neuropil disruption, and neuronal degeneration in an Atm knockout specimen. (A and B) represent two presumably consecutive phases of microglial activation associated with neuropil loss. Both panels contain a small elongated cell with numerous filiform appendages, a dark cytoplasm with lysosomes (arrow), crenated nucleolemma, and clumpy chromatin including a prominent nucleolus, i.e., features that have been correlated previously with microglia (cited in the text). Putative early stages are associated with vacuolations in the neuropil (stars) into which the filiform appendages of the microglial cells insinuate themselves (A). Presumably later stages are associated with much larger, lacune-like disruptions of the neuropil (B), which may result from the confluence of vacuoles such as those illustrated in A. C and D illustrate unequivocally degenerating neurons whose cytoplasm is severely disrupted, having lost most organelles, including mitochondria and the endoplasmic reticulum. Based on the morphological features of the normal cerebellum, the cell in C may be a Golgi neuron and that in D may be a granule neuron. Asterisks in C and D indicate vacuolations similar to those illustrated in Figs. 1 and 4, which may result from either the degeneration of the processes from the neuron in each panel or from the loss of nearby elements in the neuropil. Magnification in A and C as in D.