Chronic Temporal Lobe Epilepsy Is Associated with Enhanced Alzheimer-Like Neuropathology in 3×Tg-AD Mice
Figure 3
Neuronal and extracellular labeling with 6E10 antibody in the cortex and hippocampal formation of epileptic and control 3×Tg-AD mice at indicated ages (A–L).
6E10 IR was present in pyramidal neuron somata in deep cortical layers, amygdala, subiculum, CA1 and CA3a in normal and epileptic 3×Tg-AD mice. The antibody also visualized extracellular plaques in the subiculum, hippocampus, dentate gyrus, temporal/pyramidal cortex and amygdala in 11-monthold epileptic transgenics (B–D), but not in controls at this age (images not shown). In 14- month old controls, 6E10 labeled plaques were seen in the subiculum in caudal sections (F, arrow; shown at higher magnification in I); no plaques were seen in the hippocampal proper (E, F). In contrast, in 14-month old epileptic transgenics, plaques occurred in the subiculum, CA subfields and dentate gyrus as well as in temporal lobe cortex and amygdala (examples indicated by large arrows in G, H; H is shown at higher magnification in J–L). At higher magnification, some 6E10-labeled swollen processes were found in stratum lacunosum-moleculare (s.l.m.; K) and labeled perisomatic elements were seen around subicular and hippocampal pyramidal neurons (L, arrows). 6E10 IR was also elevated in the somata of cortical and hippocampal pyramidal neurons and the dentate granule cells in epileptics (H, J) relative to controls (F, I). Bar graphs (M–P) compare optical density measurements in selected hippocampal subregions in 9-, 11- and 14-month old mice from both groups. Quantitatively, 6E10 IR in the epileptic mice progressively increased in stratum pyramidale (s.p.; M) and stratum radiatum (s.r.)/lacunosum-moleculare (s.l.m.) of area CA1 (N), and in the dorsal subiculum (O) from 9–14 months in the epileptic mice. In addition, specific 6E10 o.d. in CA3b mossy fiber terminals (mf) in epileptics increased from 9–14 months of age and was higher relative to non-epileptic controls at each age point. Scale bar in (A) = 1 mm in (A) applying to (B, C, E–H); equivalent to 500 µm for (I, J), 200 µm for (D, K), and 100 µm for (L).