Effects of Age On Axon Terminals Forming Axosomatic Figures and Tables

Figure 1. A. Electron micrograph illustrating the morphology of an axon terminal (At) forming a symmetric synapse on the dendrite (D) of a neuron in layer 2/3 of area 46 of the cerebral cortex. The axon terminal contains pleomorphic vesicles and forms two active zones where the synaptic vesicles accumulate adjacent to the synaptic densities (arrows). B. Electron micrograph illustrating the morphology of an axon terminal (At) forming a symmetric synapse on the soma (S) of a neuron in the same cortical region. The axon terminal contains pleomorphic vesicles and forms one active zone where the synaptic vesicles accumulate adjacent to the synaptic densities (arrow). Note that the relative area covered by mitochondria is larger in the axon terminal forming the axosomatic compared to axodendritic synapse. Scale bar=1μm. Figure 2. A. Average sizes of axon terminal profiles forming axodendritic and axosomatic synapses in young and old rhesus monkeys. *indicates statistically significant differences between young and old (p<0.0001 and p=0.018 for axodendritic and axosomatic axon terminals respectively; two-tailed unpaired t-test). ¶indicates statistically significant differences between axodendritic and axosomatic for each age group (p<0.0001; two-tailed unpaired t-test). B. Average sizes of mitochondria profiles in axon terminals in young and old rhesus monkeys. *indicates statistically significant differences between young and old (p=0.0456; two-tailed unpaired ttest). Figure 3. Average percent area occupied by mitochondria relative to the size of axon terminal (AT) profiles in axodendritic and axosomatic synapses of young and old monkeys. ¶indicates statistically significant differences between axodendritic and axosomatic axon terminals in both young and old monkeys (p<0.005 for young and p<0.05 for old; two-tailed unpaired ttest). Figure 4. A. Average number of synaptic vesicle profiles per axon terminal (AT) and B. Average number of synaptic vesicle profiles per area of axon terminal profiles in young and old rhesus monkeys. *indicates statistically significant difference between axosomatic terminals in young and old monkeys (p<0.005; two-tailed unpaired t-test). ¶indicates statistically significant difference between axodendritic and axosomatic (p<0.005; two-tailed unpaired t-test). Figure 5. Linear regression analyses were carried out between the mean numbers of synaptic vesicles in axon terminals forming axosomatic synapses (A) or axodendritic synapses (B) and the cognitive impairment indices of monkeys. Results show that the severity of cognitive impairment is significantly correlated with the number of synaptic vesicles in axon terminals forming axosomatic but not axodendritic synapses (r= Pearson Correlation Coefficient). Table 1 Identification number, age and cognitive impairment index (CII) of monkeys used in this study. Monkey identification number Age (years) CII AM16 (young) 5 No data AM76 (young) 6 0.08 AM129 (young) 7 1.87 AM47 (young) 9 0.51 AM53 (young) 10 0.32 AM19 (old) 25 1.98 AM12 (old) 27 3.31 AM62 (old) 27 3.81 AM26 (old) 29 1.05 AM41 (old) 32 4.51 Table 2 Values represent the average area occupied by axon terminal and mitochondria profiles, the average numbers of synaptic vesicle profiles per axon terminal and per unit area and the average length of symmetric synaptic differentiations. The statistical significance shown is between young and old. Results from statistical analyses between axodendritic and axosomatic terminals are shown on Figures 2-4. Axodendritic Axon Terminal Size (μm2) Axosomatic Young Old Young Old 0.540 ± 0.013 0.653 ± 0.017* 0.703 ± 0.021 0.781 ± 0.022* p<0.0001 Mitochondria Size (μm2) p=0.018 n=426 n=323 n=159 n=150 0.086±0.004 0.095±0.004 0.087±0.004 0.100±0.006* n=208 n=230 n=189 n=219 54.55±2.933 57.50±3.048 48.83±2.569 59.88±2.598* p=0.0456 Synaptic Vesicle (number per terminal) p<0.005 Synaptic Vesicle number per μm2 Synaptic length (μm) n=55 n=60 n=60 n=72 81.60±3.079 73.91±3.536 67.39±3.292 66.40±2.855 n=57 n=58 n=50 n=60 0.308±0.120 0.299±0.0731 0.291±0.009 0.292±0.011 n=238 n=210 n=91 n=77