Prenatal malnutrition-induced functional alterations in callosal connections and in interhemispheric asymmetry in rats are prevented by reduction of noradrenaline synthesis during gestation.
Prenatal malnutrition results in increased concentration and release of central noradrenaline, a neurotransmitter that is an important regulator of normal regressive events such as axonal pruning and synaptic elimination. This suggests that some of the functional disturbances in brain induced by prenatal malnutrition could be due at least in part to increased noradrenaline activity that may enhance regressive events during early stages of development. To test this hypothesis we studied whether chronic administration of alpha-methyl-p-tyrosine, an inhibitor of tyrosine hydroxylase, to rats during gestation might prevent long-term deleterious effects of prenatal malnutrition on functional properties of interhemispheric connections of the visual cortex, and on asymmetry of visual evoked responses. The experiments were conducted on normal and malnourished rats 45-50 d of age. Prenatal malnutrition was induced by restricting the food consumption of pregnant rats to 40%, from d 8 postconception to parturition. At birth, prenatally malnourished rats had significantly greater whole-brain noradrenaline concentration as well as significantly enhanced noradrenaline release in the visual cortex. At 45-50 d of age, the malnourished group had a significantly smaller cortical area, exhibiting transcallosal evoked responses; in addition, the amplitude of these responses was significantly smaller. Malnourished rats showed a significant reduction of the normal interhemispheric asymmetry of visual evoked responses. The addition of 0.3% alpha-methyl-p-tyrosine to the diet of malnourished pregnant rats during the last 2 wk of gestation prevented functional disorders induced in the offspring by prenatal malnutrition on interhemispheric connectivity of visual areas and on interhemispheric bioelectrical asymmetry, probably by reducing the elevated brain noradrenaline activity and thereby restoring the normal trophic role of this neurotransmitter.
Soto-Moyano
R
R
Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, Casilla 138-11, Santiago, Chile.
Alarcon
S
S
Hernández
A
A
Pérez
H
H
Ruiz
S
S
Carreño
P
P
Kusch
C
C
Belmar
J
J
D000818:Animals; D001921:Brain / Q000378:metabolism*; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005074:Evoked Potentials, Visual; D005260:Female; D008297:Male; D009638:Norepinephrine / Q000096:biosynthesis*; D009748:Nutrition Disorders / Q000503:physiopathology*; D011247:Pregnancy; D011248:Pregnancy Complications; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors; D014793:Visual Cortex / Q000473:pathology / Q000503:physiopathology*; D015430:Weight Gain; D019805:alpha-Methyltyrosine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D019805:alpha-Methyltyrosine; D014446:Tyrosine 3-Monooxygenase; D009638:Norepinephrine