Kunio Yajima

ULTRASTRUCTURAL CHANGES OF OLIGODENDROGLIA AND MYELIN SHEATHS INDUCED BY ETHIDIUM BROMIDE

Yajima K. & Suzuki K. (1979) Neurobiology and Applied Neuropathology5, 49–62

An ultrastructural study on the cerebellum of the brindled mouse

SummaryChronological morphological alterations of the cerebellum, with particular attention to the Purkinje cells, were investigated in the brindled mottled MObr mouse, a neurological mutant mouse with close clinical similarity to Kinky hair syndrome (KHS) in humans. Seven days post-natally, slight irregularity in the morphology of mitochondria of the Purkinje cell perikarya was the only significant difference between hemizygous MObr mice and litter mate controls. With advancing age the mitochondrial change became more pronounced gradually in the former, not only in the perikarya but also in the dendrites. However, by day 31 or later the mitochondrial change subsided gradually and by day 91, the mitochondria in the majority of Purkinje cells became indistinguishable from those of littermate controls. Despite the extensive mitochondrial alteration, degeneration and necrosis of Purkinje cells were rather mild. Degeneration of white matter was quite conspicuous in the mutant mouse older than 31 days. These morphological changes of the cerebellum are compared with those of other neurological mutant mice, Nervous and Purkinje cell degeneration, and with KHS in humans.

The effect of copper supplementation on the brindled mouse: a clinico-pathological study.

Brindled mottled is a neurological mutant mouse. Hemizygous males have many clinical and biochemical features in common with kinky hair syndrome (KHS) in humans, and usually die around postnatal day 15, after severe emaciation. Neuronal mitochondrial abnormalities and neuronal degeneration in the cerebrum and cerebellum were constant neuropathological findings in this mutant. A single intraperitoneal injection of cupric chloride, 10 μg/g body weight, resulted in an improvement of clinical symptoms and prevention of neuronal degeneration. The degree of improvement was dependent on the date of injection, and day 7 or 10 postnatal appeared to be the most effective date. The male hemizygotes which received cupric chloride injections at day 7 or 10 overcame the lethality, and no neuronal degeneration was detected in these mice, although neuronal mitochondrial changes were still persistent. However, following two injections at days 7 and 10, no abnormalities were detected in the cerebral cortical neurons. Even at the ultrastructural level, abnormal mitochondria were very scarce. In the cerebellum, however, mitochondrial changes in the Purkinje cells, particularly in the rostral portion, and degeneration of white matter were noted in these mice, which were clinically perfectly healthy, judging from the growth rate and behavior. However, cerebellar changes were far less in those which received additional injections later on. These observations indicate that, at least in brindled mutant mice, supplementation of copper is quite beneficial for clinical improvement and the prevention of neuropathological lesions, but the date of administration appears to have crucial importance.

Neuronal degeneration in the brain of the brindled mouse-- a light microscope study.

The brindled mouse (Mobr) is a neurological mutant mouse with a deficiency in copper transport. This mutant has many clinical as well as biochemical features in common with Kinky hair syndrome (KHS) in humans (Tab. 1). Male hemizygotes (Mobr/Y) are characterized by the absence of fur pigment and curly whiskers. They become inactive, losing weight at around the 10th–12th post-natal day. They usually die in an emaciated state around the 15th–16th postnatal day. The brain weight is usually about three fourths of that of littermate controls. Microscopically, widespread neuronal degeneration was noted in the cerebral cortex and thalamic nuclei of male hemizygotes after the 12th post-natal day. The degeneration continued to increase until death. Scattered degenerated cells were also noted in the cerebellum. No such degenerative changes were observed in the brain of female heterozygotes (Mobr/+) or in normal or starved littermates. These degenerative changes of neurons in the brindled hemizygote mouse will be compared with the neuropathological changes observed in KHS and in experimental animals with copper deficiency, and the possible pathogenesis of these changes will be discussed.

Neuronal degeneration in the brain of the brindled mouse

SummaryBrindled mutant mouse (MObr) is clinically closely similar to kinky hair syndrome (KHS) in humans. Hemizygous males (MObr/Y) of this mutant usually cannot survive beyond the 15th–16th postnatal day. However, some were found to survive into the adult life. Extensive neuronal degeneration in the cerebral cortex was a prominent neuropathological feature of MObr/Y (Yajima and Suzuki, 1979a). In the long-surviving ones, however, such neuronal degeneration gradually disappeared and cortical neuronal loss and axonal degeneration of the underlying white matter were the predominant neuropathological features. which are closely similar to those of KHS, in particular in those patients who survive for more than 1 year. On the basis of our observations on the brain of MObr/Y mice, we hypothesized the possible chronological events on the development of neuropathological lesions in KHS in humans.

Sub-plasmalemmal linear density: A common structure in globoid cells and mesenchymal cells

SummarySub-plasmalemmal linear densities of variable length (0.1≈1.0 μ) were found to be a constant feature of globoid cells in human as well as in canine globoid cell leukodystrophy (GLD). Similar densities were also observed in experimental globoid cells and epithelioid cells in chronic granuloma but not in glial cells. The linear densities always appeared without any relation to basal laminae. These observations together with the other reports of similar structures in lymphoma, fibroma and sarcoidosis suggest that the sub-plasmalemmal density is a structure frequently observed in mesenchymal cells, and may be another supporting feature for possible mesenchymal origin of globoid cells.