Search Results - (Author, Cooperation:P. N. Hoffman)

2012-07-18

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

Amyotrophic Lateral Sclerosis/genetics/*metabolism/*pathology ; Animals ; Axons/*metabolism/pathology ; Cell Line ; Cell Survival ; Disease Models, Animal ; Down-Regulation ; Heterozygote ; Humans ; Lactic Acid/metabolism ; Mice ; Mice, Transgenic ; Monocarboxylic Acid Transporters/deficiency/genetics/*metabolism ; Motor Neurons/metabolism/*pathology ; Myelin Sheath/metabolism ; Nerve Degeneration/*metabolism ; Oligodendroglia/*metabolism ; Protein Transport ; RNA, Small Interfering ; Superoxide Dismutase/genetics/metabolism ; Symporters/deficiency/genetics/*metabolism

1471-4159

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Abstract: The immunoreactivity of the high-molecular-weight neurofilament (NF) subunit toward antibodies that react with phosphorylation-related epitopes was determined at different anatomic sites in the PNS of rats during normal maturation and after intoxication with β,β′-iminodipropionitriIe (IDPN). A maturational increase in the relative binding of phosphor-ylation-dependent antibodies compared to phosphorylation-inhibited antibodies occurred from age 3 to 12 weeks. An increase in phosphorylation-related immunoreactivity with increasing distance from the cell bodies was present in ventral and dorsal roots at all ages. The degree of phosphorylation-related immunoreactivity was greater for centrally directed axons in the dorsal roots of the L5 ganglion than for peripherally directed axons. IDPN, a toxin that impairs NF transport, caused a marked increase in reactivity toward the phos-phorylation-dependent antibody. NFs from IDPN-treated rats also bound less of an antibody that is normally phosphorylation independent and this inhibition of binding was sensitive to phosphatase digestion. In each instance, greater degrees of phosphorylation-dependent immunoreactivity correlate with conditions known to exhibit slower net rates of axonal tran; port of NF proteins

Electronic Resource

1573-7381

Springer Online Journal Archives 1860-2000

Medicine

Summary Neurofilament gene expression appears to play an important role in regulating axonal calibre. In the dorsal root ganglia of mature mammals, large sensory neurons contain high levels of neurofilament mRNAs and give rise to large-calibre myelinated axons (with diameters up to 8 μm in rat), while small sensory neurons contain undetectable levels of neurofilament mRNAs and give rise to unmyelinated axons (with diameters less than 1 μm). In the present study we used a combination of morphological and molecular approaches to examine the relationships among postnatal increases in neurofilament gene expression, growth in perikaryal size, growth in axonal calibre and myelin formation in lumbar sensory neurons of rat. Usingin situ hybridization, three populations of sensory neurons could be clearly distinguised at birth: (1) neurons containing relatively high levels of neurofilament mRNAs; (2) neurons containing low levels of neurofilament mRNAs; and (3) neurons containing undetectable levels of neurofilament mRNAs. Perikaryal size was greater for neurons with high levels of neurofilament mRNAs than for those with either low or undetectable levels. The proportion of neurons expressing high levels of neurofilament mRNAs increased from approximately 10% at birth to 30% by 28 days of age; increases in the abundance of neurofilament mRNAs in these neurons between 0 and 28 days of age, as documented by blot analyses of RNA purified from dorsal root ganglia, correlated with increases in perikaryal size. This postnatal rise in neurofilament gene expression also correlated with an increase in the cross-sectional areas of myelinated axons in the L5 dorsal root. As axons matured in their relationship to Schwann cells (polyaxonal pockets → ensheathed → segregated → myelinated), their cross-sectional areas increased. Thus, growth in both perikaryal size and axonal calibre correlated closely with increased neurofilament gene expression in these sensory neurons. These findings are consistent with the hypothesis that neurofilament expression plays an important role in the sequence of events leading to the radial growth and myelination of axons.

Electronic Resource