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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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Related in: MedlinePlus

Lack of anterior horn cell changes in old NF-deficient mice. In A–C, phase contrast images are shown of toluidine blue–stained sections of lumbar spinal cord from 2-yr-old wild-type (A), NF-M– (B), or NF-M/H– (C)  mutant animals. In D–H immunoperoxidase-stained sections of lumbar spinal cord are illustrated from wild-type (D and G), NF-M– (E and H), or NF-M/H– (F)  mutant animals stained with an NF-L antibody (D–F) or SMI-32 (G and H). No significant differences between NF-M or NF-M/H mutants and wild-type were noted. Bar, 20 μm.
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Figure 7: Lack of anterior horn cell changes in old NF-deficient mice. In A–C, phase contrast images are shown of toluidine blue–stained sections of lumbar spinal cord from 2-yr-old wild-type (A), NF-M– (B), or NF-M/H– (C) mutant animals. In D–H immunoperoxidase-stained sections of lumbar spinal cord are illustrated from wild-type (D and G), NF-M– (E and H), or NF-M/H– (F) mutant animals stained with an NF-L antibody (D–F) or SMI-32 (G and H). No significant differences between NF-M or NF-M/H mutants and wild-type were noted. Bar, 20 μm.

Mentions: The lumbar ventral roots contain axons that arise from motor neurons in the lumbar spinal cord. To determine if changes in anterior horn cells might be responsible for the axonal atrophy, spinal cord sections from the lumbar and cervical levels were examined to assess anterior horn cell morphology. Light microscopy revealed no evidence for anterior horn cell degeneration in either region in 2-yr-old NF-M– or NF-M/H– mutants (Fig. 7, A–C). Examination of lumbar spinal cord sections by electron microscopy also found no perikaryal, dendritic, or axonal abnormalities in the mutants (data not shown).


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)

Lack of anterior horn cell changes in old NF-deficient mice. In A–C, phase contrast images are shown of toluidine blue–stained sections of lumbar spinal cord from 2-yr-old wild-type (A), NF-M– (B), or NF-M/H– (C)  mutant animals. In D–H immunoperoxidase-stained sections of lumbar spinal cord are illustrated from wild-type (D and G), NF-M– (E and H), or NF-M/H– (F)  mutant animals stained with an NF-L antibody (D–F) or SMI-32 (G and H). No significant differences between NF-M or NF-M/H mutants and wild-type were noted. Bar, 20 μm.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 7: Lack of anterior horn cell changes in old NF-deficient mice. In A–C, phase contrast images are shown of toluidine blue–stained sections of lumbar spinal cord from 2-yr-old wild-type (A), NF-M– (B), or NF-M/H– (C) mutant animals. In D–H immunoperoxidase-stained sections of lumbar spinal cord are illustrated from wild-type (D and G), NF-M– (E and H), or NF-M/H– (F) mutant animals stained with an NF-L antibody (D–F) or SMI-32 (G and H). No significant differences between NF-M or NF-M/H mutants and wild-type were noted. Bar, 20 μm.
Mentions: The lumbar ventral roots contain axons that arise from motor neurons in the lumbar spinal cord. To determine if changes in anterior horn cells might be responsible for the axonal atrophy, spinal cord sections from the lumbar and cervical levels were examined to assess anterior horn cell morphology. Light microscopy revealed no evidence for anterior horn cell degeneration in either region in 2-yr-old NF-M– or NF-M/H– mutants (Fig. 7, A–C). Examination of lumbar spinal cord sections by electron microscopy also found no perikaryal, dendritic, or axonal abnormalities in the mutants (data not shown).

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