Prenatal protein restriction alters synaptic mechanisms of callosal connections in the rat visual cortex

Abstract

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.

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).…”

“…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).…”

“…Overt prenatal protein malnutrition also reduces spontaneous forebrain neuronal activity in adulthood (Stern et al, 1983). Moreover, projecting fi elds of transcallosal evoked responses are affected in overt and hidden forms of prenatal protein malnutrition (SotoMoyano et al, 1993;Soto-Moyano et al, 1998a;Forbes et al, 1975). Although reduction in CC size and functionality has been reported in malnourished animals, it has not yet been studied at the fi ne anatomical and ultrastructural levels.…”

Knockdown of α2C-adrenoceptors in the occipital cortex rescued long-term potentiation in hidden prenatally malnourished rats

“…However, this insidious form of protein maternal malnutrition, the so-called ''hidden'' prenatal malnutrition (Resnick et al, 1982), results in altered noradrenergic function in the neocortex of the offspring, as revealed by increased concentration and release of cortical noradrenaline during early postnatal life, followed by decreased cortical release of the neurotransmitter during adulthood (Soto-Moyano et al, 1998a, 1998b. In addition, these animals showed increased neocortical expression of the a 2C -adrenoceptor subtype during postnatal life (Sierralta et al, 2006;Soto-Moyano et al, 2005).…”

“…In addition, these animals showed increased neocortical expression of the a 2C -adrenoceptor subtype during postnatal life (Sierralta et al, 2006;Soto-Moyano et al, 2005). Together with the altered profile in central noradrenergic systems, the neocortex of adult prenatally malnourished animals shows weakened electrophysiological indices, including decreased ability of callosal-cortical synapses to perform temporal summation (Soto-Moyano et al, 1998a) and to maintain long-term synaptic potentiation (Hernández et al, 2008;Soto-Moyano et al, 2005).…”