Mild prenatal protein malnutrition, induced by reduction of the casein content of the maternal diet from 25 to 8%, calorically compensated by the addition of excess carbohydrates, leads to so-called "hidden" malnutrition in the rat. This form of malnutrition results in normal body and brain weights of pups at birth, but in significant alterations of their central nervous system neurochemical profiles. Since severe forms of prenatal malnutrition induce morpho-functional deficits on callosal interhemispheric communication together with brain neurochemical disturbances, we evaluated, in rats born from mothers submitted to an 8% casein diet, the potassium-induced release of [3H]-noradrenaline in visual cortex slices, as well as functional properties of callosal-cortical synapses by determining cerebral cortical excitability to callosal inputs and fatigability and temporal summation of transcallosal evoked responses. Rats born from mothers submitted to a 25% casein diet served as controls. At birth prenatally malnourished pups had significantly higher cortical percent net noradrenaline release (14.79 +/- 1.11) than controls (9.14 +/- 1.26). At 45-50 days of age, rehabilitated previously malnourished rats showed, when compared to controls; (i) significantly reduced percent net noradrenaline release in the visual cortex (4.50 +/- 0.52 vs 11.31 +/- 1.14); (ii) decreased cortical excitability to callosal inputs as revealed by significantly increased chronaxie (607.2 +/- 82.8 microseconds vs 351.3 +/- 47.7 microseconds); (iii) enhanced fatigability of transcallosal evoked responses as revealed by significantly decreased stimulus frequency required to fatigate the responses (4.9 +/- 0.8 Hz vs 9.2 +/- 1.3 Hz); and (iv) decreased ability of callosal-cortical synapses to perform temporal summation, as revealed by significantly reduced percent response increment to double-shock (54.2 +/- 6.2 vs 83.0 +/- 11.0, for a 3.2-ms interstimulus time interval). These changes, resulting from mild prenatal protein restriction, are discussed in relationship to developmental processes leading to the formation of synaptic contacts between callosal axons and their appropriate cortical target during perinatal age.

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.

It has been shown that prenatal malnutrition results at birth in increased concentration of noradrenaline (NA) in the brain. Besides, it is known that NA is an important regulator of normal regressive processes occurring during synaptogenesis such as cell death, axonal pruning and synaptic elimination. The present study was designed to investigate (i) whether prenatal malnutrition enhances the NA release in the visual cortex and (ii) whether or not chronic administration of clonidine during gestation may prevent long-term deleterious effects of fetal malnutrition on functional properties of interhemispheric connections of the visual cortex and on the interhemispheric asymmetry of visual evoked responses. Prenatal malnutrition was induced by restricting food consumption to pregnant rats from Day 8 postconception to parturition. Results show that at birth, prenatally malnourished rats had higher NA release than normals. At 45-50 days of age, the malnourished group exhibited (a) reduced peak-to-peak amplitude and diminished extent of the projecting field of transcallosal evoked responses, and (b) abolished interhemispheric asymmetry of visual evoked responses. Clonidine administration to malnourished mothers from Day 14 postconception to parturition (10 g/kg/day s.c.), prevented in the offspring disorders induced by prenatal malnutrition on cortical NA release, on interhemispheric connectivity of visual areas and on interhemispheric bioelectrical asymmetry, probably by restoring the normal trophic role of NA during synaptogenesis. Results are discussed in relationship to normal regressive events occurring during early brain development.

The effect of chronic yohimbine treatment early in life on packing density of neurons was evaluated in the occipital cortex of young rats. Yohimbine administration to pups between days 5 and 16 of postnatal life (2.5 mg/kg/day i.p.) resulted at 45 days of age in significantly higher neuronal density in layers II–V of the occipital cortex, the effect being more marked in the dorsal region than in the dorsolateral and lateral ones. Results suggest a relationship between enhanced central noradrenaline activity and altered development of the neuropil in the occipital cortex.