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

Amyotrophic lateral sclerosis is an age-related neurological disease, chara cterized by neurofilament (NF) accumulation in primary axons followed by de generation of motor neurons, To elucidate age-related factors that might le ad to pathological NF accumulation, NFs were compared between young and age d rats. Electron microscopic examination of sciatic nerve axons revealed th at NFs were more than twice as densely packed in aged rat axons (542 +/- 18 0 NFs/mm(2)) as in young adult rat axons (211 +/- 73 NFs/mm(2)), The NFs is olated from aged rats also appeared to be more aggregated than those from y oung rats, Phosphorylation at the head or tail domains was studied as a pos sible candidate affecting NF organization, Western blotting with phosphoryl ation-dependent antibodies showed higher phosphorylation of NF-H in the tai l domains of aged rat spinal cord NFs, but dephosphorylation did not dimini sh the differences in aggregation between aged and young rat NFs, On the ot her hand, when NFs were phosphorylated by A-kinase on their head domains, t he 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 possi bility that the decreased amount of NF-M induces the aggregates of isolated NFs and the higher packing density of NF in aged rat axons. (C) 1999 Wiley -Liss, Inc.