Prenatal Malnutrition-Induced Functional Alterations in Callosal Connections and in Interhemispheric Asymmetry in Rats Are Prevented by Reduction of Noradrenaline Synthesis during Gestation

Abstract

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.

Anatomy of corpus callosum in prenatally malnourished rats

“…Although the weight gain from weaning to sacrifice was significant higher in the malnourished group, no differences were observed in body weight of young rats at sacrifi ce and in the brain/body weight relation, which is in agreement with previous works by our group (Soto-Moyano et al, 1998a;Soto-Moyano et al, 1998b;Navarrete et al, 2007). Malnutrition during gestation also resulted in a signifi cant brain weight defi cit in newborns (Table I).…”

“…The experiments were conducted on male and female Sprague-Dawley rats (INTA, Santiago, Chile) born from dams subjected during pregnancy to one of the following nutritional conditions (8 pregnant rats per groups): 1) well-nourished pregnant rats, with free access to a 21% protein non purifi ed diet (Champion®, Santiago, Chile: 21.4% protein, 6.9% fat, 45.9% carbohydrate, 4.6% minerals, 0.5% vitamins, 10% water, 10.7% non-nutritive fi ller and 13.3KJ/g. ) (Soto-Moyano et al, 1998b), and 2) malnourished pregnant rats, with free access to food until 7 days post-conception; after this date the nonpurifi ed diet was restricted to 10 g/day until parturition. This amount of food is about 40% of that consumed by normal pregnant rats during weeks 2 and 3 of gestation (Soto-Moyano et al, 1993;Soto-Moyano et al, 1998b), and was given two times daily (5 g at 09:00 h and 5 g at 19:00h) in order to minimize anxiety for feeding in food restricted pregnant dams.…”

“…(Soto-Moyano et al, 1998b), and 2) malnourished pregnant rats, with free access to food until 7 days post-conception; after this date the nonpurifi ed diet was restricted to 10 g/day until parturition. This amount of food is about 40% of that consumed by normal pregnant rats during weeks 2 and 3 of gestation (Soto-Moyano et al, 1993;Soto-Moyano et al, 1998b), and was given two times daily (5 g at 09:00 h and 5 g at 19:00h) in order to minimize anxiety for feeding in food restricted pregnant dams. At birth, to ensure adequate nutrition during lactation, prenatally malnourished pups were fostered to well-nourished dams giving birth on that day, according to rearing procedures already described (Morgane et al, 1993); pups born from well-nourished mothers were also fostered to well-nourished dams, in order to equalize among groups other factors that may depend on the rearing conditions (i.e.…”

“…Body weight of pregnant rats and offspring were measured daily. All these procedures were performed as previously reported (SotoMoyano et al, 1993;Soto-Moyano et al, 1998b).…”

“…Those impairments are frequently associated to behavioral alterations (Morgane et al, 1993;Levitsky and Strupp, 1995). In addition, inadequate prenatal nutrition increases central noradrenaline levels and release (SotoMoyano et al, 1994;Soto-Moyano et al, 1998a;Soto-Moyano et al, 1998b), which is most relevant because noradrenaline is a critical factor for regulating regressive events of neuronal projections during normal brain development (Soto-Moyano et al, 1994).…”