期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 98, 期 1, 页码 307-312出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.011523698
关键词
GM1 ganglioside; ganglioside-deficient neurons; cerebellar granule neurons; neuritogenesis; intracellular calcium
资金
- NINDS NIH HHS [NS33912, R01 NS033912] Funding Source: Medline
Mice engineered to lack GM2/GD2 synthase (GalNAc-T), with resultant deficit of GM2, GD2, and all gangliotetraose gangliosides, were originally described as showing a relatively normal phenotype with only a slight reduction in nerve conduction. However, a subsequent study showed that similar animals suffer axonal degeneration, myelination defects, and impaired motor coordination. We have examined the behavior of cerebellar granule neurons from these neonatal knockouts in culture and have found evidence of impaired capacity for Ca2+ regulation. These cells showed relatively normal behavior when grown in the presence of physiological or moderately elevated K+ but gradually degenerated in the presence of high K+. This degeneration in depolarizing medium was accompanied by progressive elevation of intracellular calcium and onset of apoptosis, phenomena not observed with normal cells. No differences were detected in cells from normal vs. heterozygous mice. These findings suggest that neurons from GalNAc-T knockout mice are lacking a calcium regulatory mechanism that is modulated by one or more of the deleted gangliosides, and they support the hypothesis that maintenance of calcium homeostasis is one function of complex gangliosides during, and perhaps subsequent to, neuronal development.
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