Gestational vitamin B deficiency leads to homocysteine-associated brain apoptosis and alters neurobehavioral development in rats |
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| Authors: | Blaise Sébastien A Nédélec Emmanuelle Schroeder Henri Alberto Jean-Marc Bossenmeyer-Pourié Carine Guéant Jean-Louis Daval Jean-Luc |
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| Affiliation: | INSERM U.724, Faculté de Médecine, 9 Avenue de la Forêt de Haye, B.P. 184, 54500 Vandoeuvre-lès-Nancy, France. |
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| Abstract: | Hyperhomocysteinemia has been identified as a risk factor for neurological disorders. To study the influence of early deficiency in nutritional determinants of hyperhomocysteinemia on the developing rat brain, dams were fed a standard diet or a diet lacking methyl groups during gestation and lactation. Homocysteinemia progressively increased in the offspring of the deficient group and at 21 days reached 13.3+/-3.7 micromol/L versus 6.8+/-0.3 micromol/L in controls. Homocysteine accumulated in both neurons and astrocytes of selective brain structures including the hippocampus, the cerebellum, the striatum, and the neurogenic subventricular zone. Most homocysteine-positive cells expressed p53 and displayed fragmented DNA indicative of apoptosis. Righting reflex and negative geotaxis revealed a delay in the onset of integration capacities in the deficient group. Between 19 and 21 days, a poorer success score was recorded in deficient animals in a locomotor coordination test. A switch to normal food after weaning allowed restoration of normal homocysteinemia. Nevertheless, at 80 days of age, the exploratory behavior in the elevated-plus maze and the learning and memory behavior in the eight-arm maze revealed that early vitamin B deprivation is associated with persistent functional disabilities, possibly resulting from the ensuing neurotoxic effects of homocysteine. |
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