Neurofilaments of aged rats: the strengthened interneurofilament interaction and the reduced amount of NF-M.

Abstract:

: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/mm2) as in young adult rat axons (211 +/- 73 NFs/mm2). 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.

journal_name

J Neurosci Res

authors

Uchida A,Yorifuji H,Lee VM,Kishimoto T,Hisanaga S

keywords:

subject

Has Abstract

pub_date

1999-10-15 00:00:00

pages

337-48

issue

2

eissn

0360-4012

issn

1097-4547

pii

10.1002/(SICI)1097-4547(19991015)58:2<337::AID-JNR

journal_volume

58

pub_type

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