The effects of l-cycloserine on gangliosides in the developing mouse brain

Marked changes in ganglioside composition occur during brain development and in cultured neurons concomitant with differentiation, and maximum ganglioside synthesis occurs during neuronal maturation and synaptogenesis. These findings indicate that gangliosides probably play an important role in brain development. In this study the effects of parenterally administered l-cycloserine (an inhibitor of sphingosine synthesis) on gangliosides during the period of rapid neonatal brain growth in mice were studied. Two groups of mice (saline control and l-cycloserine-20 mg/kg/day) were treated for 8 or 16 days, starting at postnatal day 6, and sacrificed at 14, 22, 32, 62 or 110 days of age. Undernourished controls were also sacrificed at the same times. Body and cerebral weights in the l-cycloserine group were less than those of saline control animals at early ages, but the l-cycloserine animals did not show sparing of cerebral weight in relation to body weight as did the undernourished controls. Compared to saline control animals the l-cycloserine group had significantly less total lipid extract and nonlipid residue over all age groups. Animals treated with l-cycloserine had less total ganglioside NeuNAc per hemisphere, but normal concentrations on a fresh weight basis. Both groups had identical ganglioside patterns. These results indicate that although l-cycloserine does affect some aspects of brain development, it is not useful as a selective inhibitor of ganglioside synthesis in neonatal ICR Swiss Webster mice treated with a dose equivalent to the LD-17. Its value in modifying ganglioside synthesis should be viewed with caution.