Ultrastructural findings in spongy degeneration of white matter in silver foxes (Vulpes vulpes)

Abstract

Spongy degeneration of white matter in silver foxes is a naturally occurring, hereditary disorder. We report ultrastructural findings in the upper cervical cord of five perfusion-fixed foxes that were examined between 5 weeks and 2 1/4 years after the onset of clinical signs. Large cytoplasmic vacuoles in oligodendrocytes were present in the foxes examined 5, 12 and 20 weeks after the onset. Other early features of the disease were severe vacuolation of myelin sheaths, demyelination, expansion of extracellular spaces and hypertrophy of astrocytes. Evidence of partial demyelination as well as demyelination of entire internodes was found. In the later stages of the disease, the vacuolation was largely resolved but a marked astrogliosis persisted and numerous remyelinated axons were present in the gliotic areas. Vacuolation of oligodendrocytes and partial demyelination has not previously been seen together in a single disease process. The relationship between oligodendrocyte vacuolation, myelin sheath vacuolation and demyelination is discussed. It is concluded that the present condition is due to a primary damage to oligodendrocytes; however, the underlying biochemical lesion is not known.

Extensive remyelination of the CNS leads to functional recovery

“…In the Norwegian silver fox, an inherited disorder resulting in widespread vacuolation with demyelination and remyelination has been reported. However, the distribution of myelin vacuolation is different, and there are other dissimilarities from the cat disorder (19). Myelin vacuolation is a nonspecific finding seen in many other CNS pathologies, ranging from mitochondrial DNA mutations in both humans (20) and animals (21), to a wide spectrum of neurotoxic disorders including hexachlorophene and triethyltin intoxication (22).…”

A primary demyelinating disorder of young cattle

“…It is pertinent to consider a recently described inherited disease in Silver foxes (Hagen & Bjerkas, 1989;Hagen, Blakemore & Bjerkas, 1990) and draw attention to the relationship between myelin sheath vacuolation and demyelination. Whereas progression from myelin sheath vacuolation to demyelination is a feature of a number of experimental intoxications, e.g.…”

Histopathological comparison of Kearns-Sayre syndrome and PGC-1α-deficient mice suggests a novel concept for vacuole formation in mitochondrial encephalopathy

“…Helichrysum poisoning in sheep and a goat [49] Tetrapterys poisoning in sheep [35] Maple syrup urine disease in calves [31] Hereditary spongy degeneration of dogs [29], [53] Hereditary spongy degeneration of silver foxes [13] Human pathologies Aging reviewed in [34] Aspartoacylase deficiency (Canavan's disease) reviewed in [12] Hepatic encephalopathy reviewed in [12] Heroin-induced spongiform leukoencephalopathy [51] Maple syrup urine disease reviewed in [12] Mitochondrial disorders reviewed in [12] Urea cycle disorders reviewed in [12] Table II. Experimental and veterinary pathologies with oligodendroglial vacuolation…”

“…Hereditary ataxia of the rabbit [30] Hereditary spongy degeneration of silver foxes [13] in the aging brain, a frequent pathology which includes the formation of intramyelin 'balloons' due to intraperiod line splitting [34], similar to that seen in mitochondrial disorders. Our observation that aged wild-type mice also develop vacuoles to an apparently slighter extent but at the same predilection areas as their FL-PGC-1α-deficient counterparts recapitulates previous observations [10].…”