Age-Induced Loss of Mossy Fibre Synapses on CA3 Thorns in the CA3 Stratum Lucidum

Figure 3

Putative phagocytic activated microglia and altered microvascular pathology with advanced ageing in the CA3. Microvessels in the CA3 region of advanced aged animals (from 22 to 28 months old) were occasionally surrounded by perivascular cells with electron dense vesicles/lipofuscin deposits (b, d, f), compared to healthy microvessel at 4 months (a). Moreover, endothelial cell membrane lining the lumen of vessels also appeared to be structurally irregular and dysmorphic in some cases ((c, g); see arrow), with evidence of shedding of pinocytic vesicles into the lumen ((g); see arrow). There was evidence of what appeared to be leaky microvessel into the brain parenchyma ((e); see yellow demarcated line and arrow showing damage to endothelial cell membranes lining the blood vessel). On very few occasions, atherosclerotic plaques were noticeable in the lumen of a small number of microvessels with advanced ageing ((h, i); see arrow). At 12 months and more prominently at 28 months (j, k), the neuropil of the CA3-SL exhibited numerous conspicuous evidence of potentially activated microglial processes, with a dark cytoplasm, presumably full of lipofuscin deposits and spherical phagolysosomes vacuoles. Some postsynaptic structures in advanced ageing demonstrated electron dense spherical vesicles (see (k) images inset; dendrite and spine in red). Abbreviation: (Mcg) microglia in green, (Lys) phagolysosome, (Lpf) Lipofuscin, (EDV) electron dense vesicles, (P) perivascular cells (blue), (EnD) endothelial cell, (BV) blood vessel, (BL) basal lamina, (Sp) spine, (Dd) dendrite, (Ast) astrocyte, (Nu) neuronal nucleus. Scale bar represents 0.5 μm in (a–d, f, j, and k) and 2 μm in (e and g–i).