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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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Fine structure of axons in old mice with NF- mutations. Lumbar root axons from 2-yr-old wild-type (A), NF-M– (B), NF-H– (C), and NF-M/H– (D)  mutant mice are shown. In ventral roots of the NF-M– mutant (B), NFs are sparse and MTs are plentiful, whereas axoplasm of the NF-M/H mutant (D) contains only MTs. Wild-type (A) and NF-H– mutant (C) show numerous NFs and fewer MTs. Bar, 200 nm.
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Figure 3: Fine structure of axons in old mice with NF- mutations. Lumbar root axons from 2-yr-old wild-type (A), NF-M– (B), NF-H– (C), and NF-M/H– (D) mutant mice are shown. In ventral roots of the NF-M– mutant (B), NFs are sparse and MTs are plentiful, whereas axoplasm of the NF-M/H mutant (D) contains only MTs. Wild-type (A) and NF-H– mutant (C) show numerous NFs and fewer MTs. Bar, 200 nm.

Mentions: NFs were plentiful in the control and NF-H– mutant axons (Fig. 3). Also as expected, axons in the 2-yr-old NF-M/H animals were essentially devoid of NFs. Axons in atrophic roots of old NF-M– mutant animals contained relatively normal appearing NFs. However, NF numbers appeared even more dramatically depleted than in axons of young NF-M– mutants. To quantify the effect on NF number in the old NF-M– mutant, NFs were counted in the internodal regions of axons over a range of sizes and NF counts were plotted against axonal area. As shown in Fig. 4 A, axons in the mutant consistently contained vastly fewer NFs than axons in controls with the mutant axons having only ∼20% as many NFs as a comparably sized wild-type axons.


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)

Fine structure of axons in old mice with NF- mutations. Lumbar root axons from 2-yr-old wild-type (A), NF-M– (B), NF-H– (C), and NF-M/H– (D)  mutant mice are shown. In ventral roots of the NF-M– mutant (B), NFs are sparse and MTs are plentiful, whereas axoplasm of the NF-M/H mutant (D) contains only MTs. Wild-type (A) and NF-H– mutant (C) show numerous NFs and fewer MTs. Bar, 200 nm.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: Fine structure of axons in old mice with NF- mutations. Lumbar root axons from 2-yr-old wild-type (A), NF-M– (B), NF-H– (C), and NF-M/H– (D) mutant mice are shown. In ventral roots of the NF-M– mutant (B), NFs are sparse and MTs are plentiful, whereas axoplasm of the NF-M/H mutant (D) contains only MTs. Wild-type (A) and NF-H– mutant (C) show numerous NFs and fewer MTs. Bar, 200 nm.
Mentions: NFs were plentiful in the control and NF-H– mutant axons (Fig. 3). Also as expected, axons in the 2-yr-old NF-M/H animals were essentially devoid of NFs. Axons in atrophic roots of old NF-M– mutant animals contained relatively normal appearing NFs. However, NF numbers appeared even more dramatically depleted than in axons of young NF-M– mutants. To quantify the effect on NF number in the old NF-M– mutant, NFs were counted in the internodal regions of axons over a range of sizes and NF counts were plotted against axonal area. As shown in Fig. 4 A, axons in the mutant consistently contained vastly fewer NFs than axons in controls with the mutant axons having only ∼20% as many NFs as a comparably sized wild-type axons.

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