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

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.

• 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)

Chemical References

• Tumor Suppressor Protein p53
• Homocysteine

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)