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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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Hind limb paralysis in 2-yr-old NF-M/H– mutant animal. In A, a 2-yr-old NF-M/H– mutant animal is shown which exhibits a hind limb paralysis. Note the abnormal posture of the hind limbs resulting from an inability to extend the hind limbs in comparison to a wild-type mouse shown in B.
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Figure 8: Hind limb paralysis in 2-yr-old NF-M/H– mutant animal. In A, a 2-yr-old NF-M/H– mutant animal is shown which exhibits a hind limb paralysis. Note the abnormal posture of the hind limbs resulting from an inability to extend the hind limbs in comparison to a wild-type mouse shown in B.

Mentions: In contrast to the lack of neurological findings in young NF-deficient animals, four of five NF-M/H animals that have lived to 2 yr of age have developed a grossly apparent hind limb paralysis (Fig. 8). Thus, the axonal atrophy in the lumbar roots appears to be functionally significant even though no significant axonal loss or muscle atrophy is occurring.


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)

Hind limb paralysis in 2-yr-old NF-M/H– mutant animal. In A, a 2-yr-old NF-M/H– mutant animal is shown which exhibits a hind limb paralysis. Note the abnormal posture of the hind limbs resulting from an inability to extend the hind limbs in comparison to a wild-type mouse shown in B.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 8: Hind limb paralysis in 2-yr-old NF-M/H– mutant animal. In A, a 2-yr-old NF-M/H– mutant animal is shown which exhibits a hind limb paralysis. Note the abnormal posture of the hind limbs resulting from an inability to extend the hind limbs in comparison to a wild-type mouse shown in B.
Mentions: In contrast to the lack of neurological findings in young NF-deficient animals, four of five NF-M/H animals that have lived to 2 yr of age have developed a grossly apparent hind limb paralysis (Fig. 8). Thus, the axonal atrophy in the lumbar roots appears to be functionally significant even though no significant axonal loss or muscle atrophy is occurring.

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