Gestational vitamin B deficiency leads to homocysteine-associated brain apoptosis and alters neurobehavioral development in rats.
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.
Blaise
Sébastien A
SA
INSERM U.724, Faculté de Médecine, 9 Avenue de la Forêt de Haye, B.P. 184, 54500 Vandoeuvre-lès-Nancy, France.
Nédélec
Emmanuelle
E
Schroeder
Henri
H
Alberto
Jean-Marc
JM
Bossenmeyer-Pourié
Carine
C
Guéant
Jean-Louis
JL
Daval
Jean-Luc
JL
D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001522:Behavior, Animal; D001921:Brain / Q000254:growth & development / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006710:Homocysteine / Q000378:metabolism; D020138:Hyperhomocysteinemia / Q000178:diet therapy / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D018782:Maze Learning; D008568:Memory; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000178:diet therapy / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D014804:Vitamin B Deficiency / Q000150:complications / Q000178:diet therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*
D016159:Tumor Suppressor Protein p53; D006710:Homocysteine