The dorsal root ganglia in adrenomyeloneuropathy: neuronal atrophy and abnormal mitochondria.
Adrenomyeloneuropathy (AMN), a disease of spinal cord, brain, adrenal, and testis, mostly affects men with spastic paraparesis or ataxia beginning in their second or third decade. The spinal cord displays bilateral, usually symmetrical, long tract degeneration particularly of the gracile tract in a "dying-back" pattern. The available data strongly indicate that the fundamental lesion in AMN is an axonopathy or neuronopathy. We compared lumbar dorsal root ganglia (DRG) from 3 AMN patients to 6 age-matched controls histologically, morphometrically, immunohistochemically, and ultrastructurally. There was no apparent neuronal loss, necrosis or apoptosis, nor obvious atrophy; nodules of Nageotte were sparse in both groups. The morphometric studies, however, did reveal neuronal atrophy with a decrease in the number of large neurons and a corresponding increase in neurons less than 2,000 microm2, especially in the 1,500-1,999 microm2 range. No consistent immunohistochemical differences were observed, and no specific cell type appeared to be lost. Many mitochondria in the AMN neurons demonstrated lipidic inclusions; this raises the possibility that, in addition to the well-known peroxisomal defect, impaired mitochondrial function may lead to a failure of ATP-dependent axoplasmic transport in AMN spinal tracts with consequent "dying-back" axonal degeneration. The observation that the DRG parent neurons of the degenerate gracile tracts in AMN undergo atrophy and do not display appreciable evidence of cell death, even at autopsy, provides a wide window of opportunity for the development of therapeutic strategies to combat or prevent this myeloneuropathy.
Powers
J M
JM
University of Rochester Medical Center, Department of Pathology and Laboratory Medicine, New York, USA.
DeCiero
D P
DP
Cox
C
C
Richfield
E K
EK
Ito
M
M
Moser
A B
AB
Moser
H W
HW
D000326:Adrenoleukodystrophy / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D001284:Atrophy; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000378:metabolism / Q000648:ultrastructure; D050356:Lipid Metabolism; D008297:Male; D008928:Mitochondria / Q000648:ultrastructure*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D012016:Reference Values