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Neurofilaments of aged rats: The strengthened interneurofilament interaction and the reduced amount of NF‐M
Author(s) -
Uchida Atsuko,
Yorifuji Hiroshi,
Lee Virginia M.Y.,
Kishimoto Takeo,
Hisanaga Shinichi
Publication year - 1999
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19991015)58:2<337::aid-jnr14>3.0.co;2-j
Subject(s) - neurofilament , phosphorylation , amyotrophic lateral sclerosis , spinal cord , axoplasmic transport , sciatic nerve , dephosphorylation , chemistry , blot , kinase , medicine , axon , anatomy , endocrinology , microbiology and biotechnology , pathology , biology , immunohistochemistry , neuroscience , biochemistry , disease , phosphatase , gene
Amyotrophic lateral sclerosis is an age‐related neurological disease, characterized by neurofilament (NF) accumulation in primary axons followed by degeneration of motor neurons. To elucidate age‐related factors that might lead to pathological NF accumulation, NFs were compared between young and aged rats. Electron microscopic examination of sciatic nerve axons revealed that NFs were more than twice as densely packed in aged rat axons (542 ± 180 NFs/mm 2 ) as in young adult rat axons (211 ± 73 NFs/mm 2 ). The NFs isolated from aged rats also appeared to be more aggregated than those from young rats. Phosphorylation at the head or tail domains was studied as a possible candidate affecting NF organization. Western blotting with phosphorylation‐dependent antibodies showed higher phosphorylation of NF‐H in the tail domains of aged rat spinal cord NFs, but dephosphorylation did not diminish the differences in aggregation between aged and young rat NFs. On the other hand, when NFs were phosphorylated by A‐kinase on their head domains, the extent of phosphorylation in NF‐M of aged rat NFs was only one‐third of young rat NFs. We found that aged rat NFs contained only 60% of the NF‐M of young rat NFs in molar ratio compared to NF‐L. These results raise a possibility that the decreased amount of NF‐M induces the aggregates of isolated NFs and the higher packing density of NF in aged rat axons. J. Neurosci. Res. 58:337–348, 1999. © 1999 Wiley‐Liss, Inc.