Mitochondrial alterations in dorsal root ganglion cells in sporadic amyotrophic lateral sclerosis

Abstract

Little information is available regarding the morphological changes in the mitochondria in amyotrophic lateral sclerosis (ALS). In particular, mitochondrial changes in dorsal root ganglion cells have not yet been examined. We therefore conducted an electron microscopic examination of the mitochondria in dorsal root ganglion cells in 11 sporadic ALS patients, and 12 age-matched, non-neurological control individuals in order to determine whether or not they are affected in ALS. In both the controls and ALS patients, unusual inclusion bodies were frequently observed in the mitochondria in the somata of the ganglion cells. The inclusions consisted of an aggregate of tubules measuring approximately 40 nm in diameter varying in size and number. Such inclusions were frequently present in the cristae and/or intermembrane space, often expanding to form large bundles in the dilated intermembrane space. These structures quite frequently protruded outward unilaterally or bilaterally and were partially surrounded by the outer membrane of the mitochondria. The number of inclusions was significantly higher in the ALS patients than in the controls (P < 0.0001). Regularly spaced transverse processes similar to the rungs of a ladder were occasionally observed in the intermembrane space, along with infrequent but markedly increased cristae and stubby mitochondria. We concluded that mitochondrial abnormalities may be involved in the degenerative processes in the dorsal root ganglion cells in sporadic ALS. These findings therefore suggest that ALS is a widespread, more generalized disorder than previously thought, and that the degeneration is not confined to the motor neuron system.

One Universal Common Endpoint in Mouse Models of Amyotrophic Lateral Sclerosis

“…The righting reflex may also be a measure of declining proprioception. Evidence suggests the dorsal root [102], dorsal root ganglia [102], [108]–[110], dorsal funiculus [102], Clarke's nuclei [103], [109], [111], [112] and spinocerebellar tract [103], [109], [111]–[113], the regions of the spinal cord responsible for processing proprioception, may be affected in humans with ALS [103], [108]–[112] and animal models of ALS [102], [113], however some researchers failed to ascertain this association [113]. It is important to note that the magnitude of diminished proprioception and muscle loss may be different depending on the time used as the cutoff for the righting reflex, with greater atrophy of motor neurons occurring when longer cutoffs are used [113].…”

Sensory involvement in the SOD1-G93A mouse model of amyotrophic lateral sclerosis

“…We have shown some similar changes in DRG neurons, including cytoplasmic vacuolation, and mitochondrial swelling ( Figure 5). In this connection, it is worth noting that a previous study showed increased number of inclusion bodies in DRG neurons of sporadic ALS patients (Sasaki et al, 2007). The VR and DR fibers exhibited Wallerian-like degeneration: axon damage, myelin degeneration, and phagocytic cell (macrophages) infiltration into the tissues (Figure 2).…”

New Therapeutics to Modulate Mitochondrial Function in Neurodegenerative Disorders

“…Mitochondrial abnormalities are observed in the CNS of sporadic ALS subjects. In dorsal root ganglion cells, ALS subjects have a higher number of mitochondrial inclusions, which appear to consist of aggregates within the cristae and intermembrane space [279]. Further studies showed abnormal mitochondrial morphology and aggregation of mitochondria in the anterior horn of the spinal cord [280].…”