Anterior horn cells with abnormal TDP-43 immunoreactivities show fragmentation of the Golgi apparatus in ALS.
Recently, TAR DNA-binding protein of 43-kDa (TDP-43) was identified as a major component of ubiquitinated neuronal cytoplasmic inclusions observed in lower motor neurons in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitinated inclusions. We herein investigated the relationship between TDP-43 immunoreactivities and fragmentation of the Golgi apparatus (GA). Each mirror section of spinal cord tissues in 10 ALS and 3 control cases were immunostained with polyclonal anti-TDP-43 and polyclonal anti-trans-Golgi-network (TGN)-46 antibodies. The neurons were divided into subtypes according to differences in TDP-43 immunoreactivities, and we examined the morphological changes of GA in each type. We divided the neurons into four subtypes according to the observed differences in TDP-43 immunoreactivities, Type A: neurons showing normal nuclear staining, Type B: neurons showing a loss of normal nuclear staining and a few granular cytoplasmic immunoreactivities, Type C: neurons showing a lot of granular immunoreactivities and no inclusions, Type D: neurons with inclusions. All of the neurons in Type A showed normal GA profiles, however, almost all of the neurons with abnormal TDP-43 immunoreactivities (Type B-D) showed GA fragmentation. These results suggest that neurons with abnormal TDP-43 immunoreactivities are associated with dysfunction of the secretory pathway in motor neurons.
Fujita
Yukio
Y
Department of Neurology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan. yfujita@showa.gunma-u.ac.jp
Mizuno
Yuji
Y
Takatama
Masamitsu
M
Okamoto
Koichi
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000473:pathology*; D000870:Anterior Horn Cells / Q000378:metabolism / Q000648:ultrastructure*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D013116:Spinal Cord / Q000473:pathology*
D004268:DNA-Binding Proteins; D008562:Membrane Glycoproteins; C072237:TGOLN2 protein, human