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Axonal transport declines with age in two distinct phases separated by a period of relative stability.

Milde S, Adalbert R, Elaman MH, Coleman MP - Neurobiol. Aging (2014)

Bottom Line: Axonal transport also declines during normal aging, but little is known about the timing of these changes, or about the effect of aging on specific cargoes in individual axons.We also find that after tibial nerve regeneration, even in old animals, neurons are able to support higher transport rates of each cargo for a prolonged period.Thus, the age-related decline in axonal transport is not an inevitable consequence of either aging neurons or an aging systemic milieu.

View Article: PubMed Central - PubMed

Affiliation: Signalling ISP, The Babraham Institute, Babraham Research Campus, Cambridge, UK.

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Age-associated changes in NMNAT2-Venus axonal transport in sciatic nerve axons. (A) Representative straightened axon, kymograph, and kymograph of tracked particles of NMNAT2-Venus transport in sciatic nerves of 1.5- and 24-month-old NMNAT2-Venus (line 8) mice. The straightened axon represents the first frame of the time lapse recording (total 240 frames; frame rate 2 fps) that was used to generate the original kymograph. Moving particles were tracked using the ImageJ Difference Tracker set of plugins (see Table 2 for analysis parameters) and another kymograph generated to show successfully tracked particles. (B–E) Quantification of axonal transport parameters in sciatic nerve explants from NMNAT2-Venus line 8 animals of indicated ages. For all graphs, each data point represents the mean value obtained for 1 animal (5 fields of view and, on average, 14 axons per animal). Horizontal bar indicates mean, error bars are SEM. *Statistically significant difference between indicated ages or groups of ages. (*p < 0.05, **p < 0.01, ***p < 0.001, ***p < 0.0001; 1-way analysis of variance with Tukey multiple comparisons post-test or Student t test). The following parameters are shown: (B) anterograde particle velocity, (C) retrograde particle velocity, (D) anterograde particle count, and (E) retrograde particle count. (For interpretation of the references to color in this Figure, the reader is referred to the web version of this article.)
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fig1: Age-associated changes in NMNAT2-Venus axonal transport in sciatic nerve axons. (A) Representative straightened axon, kymograph, and kymograph of tracked particles of NMNAT2-Venus transport in sciatic nerves of 1.5- and 24-month-old NMNAT2-Venus (line 8) mice. The straightened axon represents the first frame of the time lapse recording (total 240 frames; frame rate 2 fps) that was used to generate the original kymograph. Moving particles were tracked using the ImageJ Difference Tracker set of plugins (see Table 2 for analysis parameters) and another kymograph generated to show successfully tracked particles. (B–E) Quantification of axonal transport parameters in sciatic nerve explants from NMNAT2-Venus line 8 animals of indicated ages. For all graphs, each data point represents the mean value obtained for 1 animal (5 fields of view and, on average, 14 axons per animal). Horizontal bar indicates mean, error bars are SEM. *Statistically significant difference between indicated ages or groups of ages. (*p < 0.05, **p < 0.01, ***p < 0.001, ***p < 0.0001; 1-way analysis of variance with Tukey multiple comparisons post-test or Student t test). The following parameters are shown: (B) anterograde particle velocity, (C) retrograde particle velocity, (D) anterograde particle count, and (E) retrograde particle count. (For interpretation of the references to color in this Figure, the reader is referred to the web version of this article.)

Mentions: To investigate age-associated changes of NMNAT2 vesicles in peripheral axons, we imaged and quantified the axonal transport of NMNAT2-Venus particles in sciatic nerve axons (Fig 1A). Average (total displacement of a particle/time tracked) and maximal (farthest displacement of each tracked particle between 2 frames) particle velocities in both anterograde and retrograde directions remained stable from 1.5 and 18 months, but then reduced significantly in animals at 24 months of age (Fig 1B and C). Surprisingly, the number of particles observed moving anterogradely and retrogradely showed a significant drop even in young animals between the ages of 3 and 6 months. This was followed by a relatively stable plateau that was maintained at least up to 18 months. From 18 to 24 months, another significant reduction in the number of anterogradely moving particles was observed, along with a similar, but statistically nonsignificant trend in the retrograde direction (Fig 1D and E). To test whether these changes could have been caused by changes in expression level of the transgene over the lifetime of the animals, which might impair tracking of particles, we quantified the average fluorescence intensity of labeled axons from animals of different ages. As shown in Table 3, there were no consistent trends or differences in fluorescence intensity that would explain the observed changes in the number of moving particles.


Axonal transport declines with age in two distinct phases separated by a period of relative stability.

Milde S, Adalbert R, Elaman MH, Coleman MP - Neurobiol. Aging (2014)

Age-associated changes in NMNAT2-Venus axonal transport in sciatic nerve axons. (A) Representative straightened axon, kymograph, and kymograph of tracked particles of NMNAT2-Venus transport in sciatic nerves of 1.5- and 24-month-old NMNAT2-Venus (line 8) mice. The straightened axon represents the first frame of the time lapse recording (total 240 frames; frame rate 2 fps) that was used to generate the original kymograph. Moving particles were tracked using the ImageJ Difference Tracker set of plugins (see Table 2 for analysis parameters) and another kymograph generated to show successfully tracked particles. (B–E) Quantification of axonal transport parameters in sciatic nerve explants from NMNAT2-Venus line 8 animals of indicated ages. For all graphs, each data point represents the mean value obtained for 1 animal (5 fields of view and, on average, 14 axons per animal). Horizontal bar indicates mean, error bars are SEM. *Statistically significant difference between indicated ages or groups of ages. (*p < 0.05, **p < 0.01, ***p < 0.001, ***p < 0.0001; 1-way analysis of variance with Tukey multiple comparisons post-test or Student t test). The following parameters are shown: (B) anterograde particle velocity, (C) retrograde particle velocity, (D) anterograde particle count, and (E) retrograde particle count. (For interpretation of the references to color in this Figure, the reader is referred to the web version of this article.)
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Related In: Results  -  Collection

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Show All Figures
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fig1: Age-associated changes in NMNAT2-Venus axonal transport in sciatic nerve axons. (A) Representative straightened axon, kymograph, and kymograph of tracked particles of NMNAT2-Venus transport in sciatic nerves of 1.5- and 24-month-old NMNAT2-Venus (line 8) mice. The straightened axon represents the first frame of the time lapse recording (total 240 frames; frame rate 2 fps) that was used to generate the original kymograph. Moving particles were tracked using the ImageJ Difference Tracker set of plugins (see Table 2 for analysis parameters) and another kymograph generated to show successfully tracked particles. (B–E) Quantification of axonal transport parameters in sciatic nerve explants from NMNAT2-Venus line 8 animals of indicated ages. For all graphs, each data point represents the mean value obtained for 1 animal (5 fields of view and, on average, 14 axons per animal). Horizontal bar indicates mean, error bars are SEM. *Statistically significant difference between indicated ages or groups of ages. (*p < 0.05, **p < 0.01, ***p < 0.001, ***p < 0.0001; 1-way analysis of variance with Tukey multiple comparisons post-test or Student t test). The following parameters are shown: (B) anterograde particle velocity, (C) retrograde particle velocity, (D) anterograde particle count, and (E) retrograde particle count. (For interpretation of the references to color in this Figure, the reader is referred to the web version of this article.)
Mentions: To investigate age-associated changes of NMNAT2 vesicles in peripheral axons, we imaged and quantified the axonal transport of NMNAT2-Venus particles in sciatic nerve axons (Fig 1A). Average (total displacement of a particle/time tracked) and maximal (farthest displacement of each tracked particle between 2 frames) particle velocities in both anterograde and retrograde directions remained stable from 1.5 and 18 months, but then reduced significantly in animals at 24 months of age (Fig 1B and C). Surprisingly, the number of particles observed moving anterogradely and retrogradely showed a significant drop even in young animals between the ages of 3 and 6 months. This was followed by a relatively stable plateau that was maintained at least up to 18 months. From 18 to 24 months, another significant reduction in the number of anterogradely moving particles was observed, along with a similar, but statistically nonsignificant trend in the retrograde direction (Fig 1D and E). To test whether these changes could have been caused by changes in expression level of the transgene over the lifetime of the animals, which might impair tracking of particles, we quantified the average fluorescence intensity of labeled axons from animals of different ages. As shown in Table 3, there were no consistent trends or differences in fluorescence intensity that would explain the observed changes in the number of moving particles.

Bottom Line: Axonal transport also declines during normal aging, but little is known about the timing of these changes, or about the effect of aging on specific cargoes in individual axons.We also find that after tibial nerve regeneration, even in old animals, neurons are able to support higher transport rates of each cargo for a prolonged period.Thus, the age-related decline in axonal transport is not an inevitable consequence of either aging neurons or an aging systemic milieu.

View Article: PubMed Central - PubMed

Affiliation: Signalling ISP, The Babraham Institute, Babraham Research Campus, Cambridge, UK.

Show MeSH
Related in: MedlinePlus