Related Experiment Videos
Abnormalities of Purkinje cell arborization in brindled mouse cerebellum. A Golgi study
Abstract:
The cerebellum of the hemizygous brindled mouse (MObr/y), a murine model of Kinky hair disease (KHD) in human beings, was investigated chronologically using the Golgi technique. In 15-day-old MObr/y, Purkinje cells showed considerable changes in their arborization such as perisomatic dendrite-like processes, numerous spine-like protrusions from somata and stem dendrites, focal swellings of stem and distal dendrites and generally poor development of dendritic trees. These changes closely resembled those of KHD. Similar changes except for the focal swellings of dendrites, could be found in control mice at day eight but never after day 12. In the MObr/y receiving intraperitoneal injections of cupric chloride (CuCl2) on postnatal (PN) days seven and ten, Purkinje cells appeared similar, if not identical, to those of controls at PN day 15. Focal swellings of dendrites transiently reappeared in treated animals after PN day 23 but spontaneously subsided by day 110. These results suggested that normal arborization of Purkinje cells in MObr/y is at least in part due to delayed maturation, which is correctable by cupric chloride (CuCl2) treatment. The "weeping willow" deformity, which characterizes Purkinje cells in KHD in humans were not observed in MObr/y. Because other neuronal populations, which are known to be deficient in KHD, appeared well preserved in the murine mutant, these dendritic deformities may be secondary to the loss of other neurons.
Insights
The brindled mouse model of Kinky hair disease shows Purkinje cell abnormalities, but copper treatment corrects these cerebellar defects. This suggests delayed maturation is key and treatable in Kinky hair disease (KHD).
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Kinky hair disease (KHD) is a genetic disorder affecting copper metabolism.
- The hemizygous brindled mouse (MObr/y) serves as a model for KHD.
- Purkinje cells in the cerebellum are crucial for motor control and are affected in KHD.
Purpose of the Study:
- To investigate the chronological changes in Purkinje cell arborization in the MObr/y mouse model.
- To determine if copper supplementation can correct these developmental abnormalities.
- To understand the underlying mechanisms of Purkinje cell dysfunction in KHD.
Main Methods:
- Golgi staining technique was used for detailed morphological analysis of Purkinje cells.
- Chronological investigation of cerebellar development in MObr/y mice from postnatal day 8 to 110.
- Treatment with cupric chloride (CuCl2) in MObr/y mice to assess its therapeutic effect.
Main Results:
- MObr/y mice at 15 days old exhibited significant Purkinje cell dendritic abnormalities, mimicking KHD.
- Cupric chloride treatment normalized Purkinje cell morphology in MObr/y mice by postnatal day 15.
- While some abnormalities transiently reappeared, they resolved by day 110, indicating a correctable developmental delay.
Conclusions:
- The observed Purkinje cell defects in MObr/y mice are likely due to delayed maturation.
- Cupric chloride treatment effectively corrects these developmental abnormalities, suggesting a therapeutic potential for KHD.
- The absence of the 'weeping willow' deformity and preservation of other neuronal populations suggest specific, rather than global, neuronal deficits in this model.