STUDIES ON BRAIN GANGLIOSIDES: IV. THE EFFECT OF HYPERCAPNIA ON GANGLIOSIDES IN VIVO

Abstract

Gangliosides are relatively stable acidic glycolipid components of neuronal membranes. When isolated and purified from normal human, rat, or cat brains, they contain 1 μmole of N-acetylneuraminic acid (NANA) per mg. Gangliosides, isolated and purified from fresh autopsy specimens of human brain of patients who were cyanotic before death, contained considerably less NANA and N-acetyl-galactosamine than normal brain gangliosides. Also, gangliosides isolated from cerebral tissue adjacent to a variety of intracerebral lesions contained less NANA than gangliosides from uninvolved tissue from the same patient. Gangliosides from the brains of cats which had been asphyxiated for periods up to 8 minutes also contained less NANA and hexosamine. Experiments in which cats were treated with various gas mixtures showed that hypercapnia and the consequent respiratory acidosis were the major causes of the change in ganglioside composition in vivo. Treatment with 100% N2produced a respiratory alkalosis but had no effect on brain ganglioside composition. The mechanism by which hypercapnia causes the change in the composition of the membrane gangliosides is unclear. An intact cerebral circulation appeared necessary to elicit the changes. The possibility that hypercapnia releases enzyme activators (e.g. adrenalin) or activates brain glycosidases is discussed. The loss of anionic groups located in the neuronal membrane would alter the behavior of these lipids towards cations and may, in part, explain the altered excitability of neurones following hypercapnia.