Gestational vitamin B deficiency leads to homocysteine-associated brain apoptosis and alters neurobehavioral development in rats - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue American Journal of Pathology Année : 2007

Gestational vitamin B deficiency leads to homocysteine-associated brain apoptosis and alters neurobehavioral development in rats

Sébastien Blaise
Jean-Marc Alberto
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Carine Bossenmeyer-Pourié
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Jean-Luc Daval
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Résumé

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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RAT

Dates et versions

hal-00466548 , version 1 (24-03-2010)

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Citer

Sébastien Blaise, Emmanuelle Nédélec, Henri Schroeder, Jean-Marc Alberto, Carine Bossenmeyer-Pourié, et al.. Gestational vitamin B deficiency leads to homocysteine-associated brain apoptosis and alters neurobehavioral development in rats. American Journal of Pathology, 2007, 170 (2), pp.667-79. ⟨10.2353/ajpath.2007.060339⟩. ⟨hal-00466548⟩
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