Abnormal cellular translocation of α‐internexin in spinal motor neurons of Dystonia musculorum mice

Abstract

Dystonia musculorum (dt) is a mutant mouse with hereditary neuropathy where the dysfunction is mainly found in the dorsal root ganglia (DRG) neurons but not in the spinal motor neurons. However, the accumulation of intermediate filament (IF) proteins in the swelling axons of spinal motor neurons could be found in dt/dt mice. In order to understand the pathological role of neuronal IFs in the swelling axons of spinal motor neurons from dt/dt mice, we extensively examined the distribution of neuronal IF proteins. By immunofluorescence staining, our results indicated that alpha-internexin was a major component in the swelling axon and showed abnormal translocation in the nuclei of spinal motor neurons in dt/dt mice. This abnormal translocation of alpha-internexin in the nuclei of spinal motor neurons was also confirmed by Western blotting and immunoelectron microscopy. Instead of the 10-nm filamentous structure, a diffuse immunopositive pattern of alpha-internexin was observed in the nucleus of spinal motor neurons in dt/dt mutants. We further examined the cell death of spinal motor neurons by TUNEL assay, and no TUNEL-positive cells could be identified from spinal motor neurons in dt/dt mice. From these observations we suggest that abnormal accumulation of neuronal IFs in the swelling axons and abnormal translocation of alpha-internexin in the nuclei of the spinal motor neurons from dt/dt mice may not directly cause cell death of the spinal motor neurons.

Vitamin D receptor and enzyme expression in dorsal root ganglia of adult female rats: Modulation by ovarian hormones

“…Chicken IgY anti-peripherin AB9282 (Millipore, Billerica, MA) was raised against recombinant peripherin protein and rabbit anti-peripherin AB1530 (Millipore, Billerica, MA) was raised against a trp-E fusion protein containing all but the four N-terminal amino acids. The rabbit anti-peripherin antibody has been previously characterized (Tseng et al , 2008), and the percentage of DRG neurons expressing peripherin was similar to other accounts (Table 1) (Goldstein et al , 1991). Double staining of DRG with both the chicken and rabbit antibodies revealed identical staining patterns.…”

Levels of Cocaine- and Amphetamine-Regulated Transcript in Vagal Afferents in the Mouse Are Unaltered in Response to Metabolic Challenges

“…Lysates from cell lines transfected with the peripherin gene also showed a single band at approximately 58 kDa (Tseng et al, 2008; Xiao et al, 2008). Moreover, it was shown that the staining obtained with this antibody overlapped perfectly with that of eGFP-peripherin in PC12 cells (Tseng et al, 2008). As anticipated, this antibody produced filamentous staining of the neuronal perikarya in the nodose ganglion.…”

Neuronal degeneration in autonomic nervous system of Dystonia musculorum mice

“…However, morphometric study has shown sensory innervations is significantly reduced in dt/dt mutants [3,5,7,8]. This study indicates that the sensory nerve is not only markedly denervated in the cutaneous part of footpads, but that sympathetic innervation is also severely impaired in sweat glands of young adult dt/dt mice.…”

“…Most previous studies on neuronal degeneration in dt/dt mice focused on the sensory nerve system [3,5], whereas the autonomic nervous system was seldom addressed. In our previous study of spinal motor neurons in dt/dt mice, no significant neuronal loss was observed in the spinal motor neurons [8]. However, the lifespan of these homozygous mutants is limited to three to four months.…”

“…Previous studies have demonstrated substantial degenerative alterations involving the peripheral and central sensory pathways, and spinal motor neurons are slightly affected [5]. This pathology appears primarily related to abnormal axonal accumulations of cytoskeleton in dt/dt mice [5-8]. …”