Neurotoxic effects of 6-aminonicotinamide on cultures of central nervous tissue.

Abstract

Well myelinated cultures of chick embryo spinal cord were exposed to medium containing 6-aminonicotinamide in a concentration of 0.5 mmol for up to 48 h. By 24–48 h of exposure to the antivitamin, neurons showed a granulovacuolar degeneration which later led to the formation of large vacuoles in the neuronal perikarya. Myelin degeneration was also observed in this period in the form of swelling, beading and ballooning. Electron microscopy revealed moderately swollen mitochondria and dilated endoplasmic reticulum as the earliest neuronal change. Later, neurons became pyknotic and the cytoplasmic organelles disintegrated. Presynaptic endings and glial cells, however, was spared any degenerative change. Intermittent and irregular splitting of myelin lamellae were also observed along the intraperiod lines. Biochemical assay of the glucose-6-phosphate dehydrogenase activity in the experimental cultures showed that 45% of the enzyme activity was lost during the 30-h period. It is concluded that the formation of 6-aminonicotinamide analogues of NAD and NADP coenzymes leads to the impairment of the pentose phosphate pathway and the glucose turnover, and thus produces neurotoxic effects in the central nervous system.