Vitamin B 12 and the lipids of the central nervous system

Abstract

Summary A vitamin B12 deficient diet containing antibiotic to inhibit intestinal flora and endogenous B12 was fed to female Wistar rats for four weeks. The rats were then bred and the newborn were divided into two groups one of which continued to receive the B12 deficient antibiotic supplemented regimen. The second group was fed the identical diet plus vitamin B12 (Merck Sharp and Dohme). This group served as a control to the experimental group with which they were paired. Attempts to produce a B12 deficiency with neurological complications such as subacute combined degeneration of the spinal cord, have not been successful in rats. It was postulated that maternal dietary deficiency of B12 would sufficiently deprive the fetus during the period of maximum growth and nutritional demand, to result in initial nerve damage such that a lesion resembling the histology observed in pernicious anaemia in man would result if the newborn were continued on the B12 deficient diet in the postnatal period. B12 concentration of brain, spinal cord, sciatic nerve, plasma, spleen, liver, and kidney was measured at four, eight, and twelve months of age. Lipid analyses were confined to brain, spinal cord, and sciatic nerve tissue. B12 concentration was markedly diminished in all tissues of the deficient animals, compared to the controls, and weight gain was greatly reduced. At four months of age a marked decrease in the cephalin and lecithin fractions of the brain and spinal cord was observed in the B12 deficient animals. No additional fall occurred at eight and twelve months of age. The triglyceride concentration of sciatic nerve was markedly decreased during the entire study. Gas chromatography analysis of the total lipid extracts from these tissues showed the fatty acids were not significantly different between the test and control groups in any period. 7.Histological examination failed to show any change in the myelin. The administration of inorganic phosphorus (P32) eight days prior to terminating each experimental period indicated decreased incorporation of P32 into all of the phospholipids. Vitamin B12 deficiency in rats from the fetal stage for one year failed to produce any clinical symptoms in the rat resembling those observed in B12 deficiency in man. Significant changes in the phospholipid fractions were not coincident with measurable clinical symptoms suggesting that the biochemical lesion must be extensive to produce symptoms and must precede the clinical findings by a lengthy period of time.