Spinal anterior horn cells in sporadic amyotrophic lateral sclerosis show ribosomal detachment from, and cisternal distention of the rough endoplasmic reticulum

Aims: Sporadic amyotrophic lateral sclerosis (ALS) is a progressive and invariably fatal disease involving the upper and lower motor neurones of adult humans. Among the neuropathological features of the disease, abnormalities in the protein-synthesizing system in motor neurones of the brainstem and spinal cord, such as a decrease of cytoplasmic RNA and rough endoplasmic reticulum (rER) (chromatolysis), defective editing of the Q/R site of the glutamate receptor subunit GluR2 mRNA, fragmentation of the Golgi apparatus and accumulation of ubiquitinated inclusions and abnormal TdP-43 protein have been reported to be essential for the degeneration. In relation to these features, although the possibility of ER stress has been reported in motor neurones of the brainstem and spinal cord of ALS patients, the rER itself has not been a main target of ultrastructural investigation. Methods: The present study examined the rER, ultrastructurally and quantitatively in the spinal anterior horn cells (AHCs) of 21 Japanese patients with sporadic ALS and eight Japanese control subjects. Results and conclusions: It was found that: (i) the rER cisternae in AHCs showing central chromatolysis were fragmented, but retained their width and had normally attached ribosomes, and (ii) the rER cisternae in shrunken AHCs were irregularly distended with detachment of the ribosomes, thus suggesting that (iii) ribosomal detachment was related to rER distention.