Golgi study on macular mutant mouse after copper therapy
H Kawasaki1, T Yamano, S Iwane
1Department of Pediatrics, Shiga University of Medical Science, Japan.
Abstract:
This study was undertaken to elucidate the clinical and neuropathological effects of copper administration on the macular mutant mouse. Its hemizygote, which is considered to be a model of Menkes kinky hair disease (MKHD), was injected intraperitoneally four times with 10, 20, 20 and 30 micrograms of cupric chloride on days 4, 6, 8 and 10, respectively. The hemizygote's curly whiskers gradually straightened and the frequent tonic seizures and ataxia disappeared after the injections. The body weight also gradually increased. In the cerebral cortex, the dendritic arborization of the pyramidal neurons in both the normal littermate and the treated hemizygote developed with time and reached the maximum around day 60. In the treated hemizygote, however, the arborization of the dendrites was significantly poor in comparison with that in the normal littermate from day 20 to 90. In the cerebellum of the treated hemizygote, the abnormal Purkinje cells with the few somal sprouts, thick stem dendrite and/or poor arborization, which were seen in the non-treated hemizygote, were improved by day 30, while their focal dendritic swellings remained even on day 60. These results indicate that the copper therapy improves not only the clinical manifestations but also the neuropathological changes, especially in the cerebellum.
Insights
Copper therapy improved Menkes kinky hair disease (MKHD) mouse models by correcting clinical symptoms and enhancing neuropathological changes, particularly in the cerebellum. This treatment offers potential for managing this genetic disorder.
Area of Science:
- Neuroscience
- Genetics
- Biochemistry
Background:
- Menkes kinky hair disease (MKHD) is a genetic disorder affecting copper metabolism.
- The macular mutant mouse hemizygote serves as a model for MKHD.
- Neuropathological deficits are a hallmark of MKHD.
Purpose of the Study:
- To investigate the effects of copper administration on a mouse model of MKHD.
- To assess both clinical and neuropathological outcomes following copper treatment.
- To determine the efficacy of copper therapy in ameliorating MKHD symptoms.
Main Methods:
- Intraperitoneal injections of cupric chloride were administered to macular mutant mouse hemizygotes at specific dosages and intervals.
- Clinical observations included monitoring whisker morphology, seizures, ataxia, and body weight.
- Neuropathological analysis focused on dendritic arborization of pyramidal neurons in the cerebral cortex and Purkinje cells in the cerebellum.
Main Results:
- Copper treatment led to the straightening of curly whiskers, disappearance of seizures and ataxia, and increased body weight in the treated hemizygotes.
- While dendritic arborization improved over time in both normal and treated mice, it remained poorer in treated hemizygotes compared to controls.
- Abnormal Purkinje cells in the cerebellum showed improvement, though focal dendritic swellings persisted.
Conclusions:
- Copper therapy effectively ameliorates clinical manifestations in the MKHD mouse model.
- Neuropathological changes, especially in the cerebellum, are partially reversed by copper administration.
- Copper treatment demonstrates therapeutic potential for Menkes kinky hair disease.
