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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Authors | Sébastien A Blaise, Emmanuelle Nédélec, Henri Schroeder, Jean-Marc Alberto, Carine Bossenmeyer-Pourié, Jean-Louis Guéant, Jean-Luc Daval |
Journal | The American journal of pathology
(Am J Pathol)
Vol. 170
Issue 2
Pg. 667-79
(Feb 2007)
ISSN: 0002-9440 [Print] United States |
PMID | 17255334
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Tumor Suppressor Protein p53
- Homocysteine
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Topics |
- Animals
- Apoptosis
- Astrocytes
(metabolism, pathology)
- Behavior, Animal
- Brain
(growth & development, metabolism, pathology, physiopathology)
- Female
- Homocysteine
(metabolism)
- Hyperhomocysteinemia
(diet therapy, etiology, metabolism, pathology, physiopathology)
- Maze Learning
- Memory
- Neurons
(metabolism, pathology)
- Pregnancy
- Pregnancy Complications
(diet therapy, metabolism, physiopathology)
- Rats
- Rats, Wistar
- Time Factors
- Tumor Suppressor Protein p53
(biosynthesis)
- Vitamin B Deficiency
(complications, diet therapy, metabolism, pathology, physiopathology)
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