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Age-related atrophy of motor axons in mice deficient in the mid-sized neurofilament subunit.

Elder GA, Friedrich VL, Margita A, Lazzarini RA - J. Cell Biol. (1999)

Bottom Line: The atrophic process is not accompanied by significant axonal loss or anterior horn cell pathology.By contrast, the preserved dorsal root axons of NF-M- mutant animals do not show a similar depletion of neurofilaments.These studies argue that neurofilaments are necessary for the structural maintenance of some populations of axons during aging and that the NF-M subunit is especially critical.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA.

ABSTRACT
Neurofilaments are central determinants of the diameter of myelinated axons. It is less clear whether neurofilaments serve other functional roles such as maintaining the structural integrity of axons over time. Here we show that an age-dependent axonal atrophy develops in the lumbar ventral roots of mice with a mutation in the mid-sized neurofilament subunit (NF-M) but not in animals with a mutation in the heavy neurofilament subunit (NF-H). Mice with mutations in both genes develop atrophy in ventral and dorsal roots as well as a hind limb paralysis with aging. The atrophic process is not accompanied by significant axonal loss or anterior horn cell pathology. In the NF-M- mutant atrophic ventral root, axons show an age-related depletion of neurofilaments and an increased ratio of microtubules/neurofilaments. By contrast, the preserved dorsal root axons of NF-M- mutant animals do not show a similar depletion of neurofilaments. Thus, the lack of an NF-M subunit renders some axons selectively vulnerable to an age-dependent atrophic process. These studies argue that neurofilaments are necessary for the structural maintenance of some populations of axons during aging and that the NF-M subunit is especially critical.

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Microtubule content in aging NF-M–deficient animals. (A) MTs were counted in the same axons as in Figure 4 A. Note the relatively increased numbers of MTs in the NF-M– mutant. Regression equations:  for wild-type  and .  for effect of genotype on combined slope plus intercept. (B) The ratio of MTs/NFs is shown for axons of the indicated genotypes and ages. Note the increasing ratio of MTs/NFs with age in the ventral roots of NF-M– mutant animals. Data for ventral roots from 4-mo-old wild-type and NF-M mutant are taken from Elder et al. 1998a.
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Figure 5: Microtubule content in aging NF-M–deficient animals. (A) MTs were counted in the same axons as in Figure 4 A. Note the relatively increased numbers of MTs in the NF-M– mutant. Regression equations: for wild-type and . for effect of genotype on combined slope plus intercept. (B) The ratio of MTs/NFs is shown for axons of the indicated genotypes and ages. Note the increasing ratio of MTs/NFs with age in the ventral roots of NF-M– mutant animals. Data for ventral roots from 4-mo-old wild-type and NF-M mutant are taken from Elder et al. 1998a.

Mentions: By contrast, these same axons contained relatively more MTs. Axons in the NF-M– mutant contained nearly double the number of MTs found in comparably sized wild-type axons (Fig. 5 A), increasing the average ratio of MTs to NFs from 0.18 ± 0.9 (SD) in wild-type to 1.57 ± 1.13 in the mutant axons (P < 0.0001, see Fig. 5 B and Table ). By comparison, MT to NF ratios in 4-mo-old NF-M– mutants increase from 0.22 in wild-type to 0.83 in mutant axons (Elder et al. 1998a).


Age-related atrophy of motor axons in mice deficient in the mid-sized neurofilament subunit.

Elder GA, Friedrich VL, Margita A, Lazzarini RA - J. Cell Biol. (1999)

Microtubule content in aging NF-M–deficient animals. (A) MTs were counted in the same axons as in Figure 4 A. Note the relatively increased numbers of MTs in the NF-M– mutant. Regression equations:  for wild-type  and .  for effect of genotype on combined slope plus intercept. (B) The ratio of MTs/NFs is shown for axons of the indicated genotypes and ages. Note the increasing ratio of MTs/NFs with age in the ventral roots of NF-M– mutant animals. Data for ventral roots from 4-mo-old wild-type and NF-M mutant are taken from Elder et al. 1998a.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199745&req=5

Figure 5: Microtubule content in aging NF-M–deficient animals. (A) MTs were counted in the same axons as in Figure 4 A. Note the relatively increased numbers of MTs in the NF-M– mutant. Regression equations: for wild-type and . for effect of genotype on combined slope plus intercept. (B) The ratio of MTs/NFs is shown for axons of the indicated genotypes and ages. Note the increasing ratio of MTs/NFs with age in the ventral roots of NF-M– mutant animals. Data for ventral roots from 4-mo-old wild-type and NF-M mutant are taken from Elder et al. 1998a.
Mentions: By contrast, these same axons contained relatively more MTs. Axons in the NF-M– mutant contained nearly double the number of MTs found in comparably sized wild-type axons (Fig. 5 A), increasing the average ratio of MTs to NFs from 0.18 ± 0.9 (SD) in wild-type to 1.57 ± 1.13 in the mutant axons (P < 0.0001, see Fig. 5 B and Table ). By comparison, MT to NF ratios in 4-mo-old NF-M– mutants increase from 0.22 in wild-type to 0.83 in mutant axons (Elder et al. 1998a).

Bottom Line: The atrophic process is not accompanied by significant axonal loss or anterior horn cell pathology.By contrast, the preserved dorsal root axons of NF-M- mutant animals do not show a similar depletion of neurofilaments.These studies argue that neurofilaments are necessary for the structural maintenance of some populations of axons during aging and that the NF-M subunit is especially critical.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA.

ABSTRACT
Neurofilaments are central determinants of the diameter of myelinated axons. It is less clear whether neurofilaments serve other functional roles such as maintaining the structural integrity of axons over time. Here we show that an age-dependent axonal atrophy develops in the lumbar ventral roots of mice with a mutation in the mid-sized neurofilament subunit (NF-M) but not in animals with a mutation in the heavy neurofilament subunit (NF-H). Mice with mutations in both genes develop atrophy in ventral and dorsal roots as well as a hind limb paralysis with aging. The atrophic process is not accompanied by significant axonal loss or anterior horn cell pathology. In the NF-M- mutant atrophic ventral root, axons show an age-related depletion of neurofilaments and an increased ratio of microtubules/neurofilaments. By contrast, the preserved dorsal root axons of NF-M- mutant animals do not show a similar depletion of neurofilaments. Thus, the lack of an NF-M subunit renders some axons selectively vulnerable to an age-dependent atrophic process. These studies argue that neurofilaments are necessary for the structural maintenance of some populations of axons during aging and that the NF-M subunit is especially critical.

Show MeSH
Related in: MedlinePlus