Motor neurons are rich in non-phosphorylated neurofilaments: cross-species comparison and alterations in ALS.
The localization and distribution of non-phosphorylated neurofilaments (NP-NF) in the upper and lower motor neurons was investigated in the rat, the common marmoset, the rhesus monkey and man using the SMI-32 antibody. Within the spinal cord of all species studied, the most intense NP-NF immunoreactivity was observed within the ventral horn alpha-motor neurons. Concurrent staining for the cholinergic marker choline acetyltransferase (ChAT) demonstrated that virtually all of the ChAT-positive alpha-motor neurons contain NP-NF immunoreactivity. Although NP-NF staining was also observed in other neurons within the ventral and intermediate horns, these neurons were loosely scattered and contained a considerably lower staining intensity. The only other prominent NP-NF staining in the spinal cord occurred within the neurons of the dorsal nucleus of Clark and the intermediolateral cell column. Phosphorylated neurofilament (P-NF) immunoreactivity was found primarily in neuronal processes. Occasionally, a solitary motor neuron contained weak P-NF immunoreactivity. Within the brainstem, neurons in all cranial nerve motor nuclei contained intense NP-NF immunoreactivity. The distribution and apparent density of NP-NF immunoreactive neurons in these nuclei was virtually identical to that observed for neurons immunoreactive for ChAT. NP-NF immunoreactive neurons of relatively lower intensity were found in many other regions of the brainstem. All of the giant Betz cells of layer (L) V in the motor cortex contained dark NP-NF immunoreactivity. Within the spinal cord of amyotrophic lateral sclerosis (ALS) patients, both Nissl and NP-NF staining demonstrated the dramatic loss of alpha-motor neurons characteristic of this disorder. Some of the remaining motor neurons contained intense P-NF immunoreactivity. These observations suggest that NP-NF immunoreactivity is a good marker for motor neurons in health and disease and may be a useful tool for studies of motor neuron degeneration (MND).
Tsang
Y M
YM
Laboratory for Neurodegenerative and Aging Research, Department of Medicine, Harvard Medical School and Section of Gerontology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Chiong
F
F
Kuznetsov
D
D
Kasarskis
E
E
Geula
C
C
D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D000818:Animals; D001933:Brain Stem / Q000737:chemistry; D002144:Callithrix; D002795:Choline O-Acetyltransferase / Q000032:analysis*; D006801:Humans; D008253:Macaca mulatta; D009044:Motor Cortex / Q000737:chemistry; D009046:Motor Neurons / Q000737:chemistry*; D016900:Neurofilament Proteins / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
D016900:Neurofilament Proteins; D002795:Choline O-Acetyltransferase