Long-term Consequences of Early Undernourishment on the Activation of Brain Serotonin Synthesis in the Rat: Effect of Nutritional Recovery during the Period of Nursing

Abstract

In the present study we report that the undernourished rats during fetal life submitted to a neonatal recovery regime had a return to normal metabolic and physical growth conditions during the nursing period, and that their food consumption was more than controls, from weaning until adult age. However, in spite of the metabolic and physical recovery of the gestational undernourished rats, the activity of brain tryptophan-5-hydroxylase (TrpOH) remained elevated accompanied by an increase in the concentration of the neurotransmitter, serotonin (5-HT). Besides, the current observation confirms and extends to previous results, that an increase in brain 5-HT content, in L-tryptophan (L-Trp) concentration and in the activity of TrpOH, in undernourished rats occurs not only during gestation and lactation periods, but it lasts until adulthood. The increase in the activity of TrpOH observed during the fetal stage and continuing to postnatal life in undernourished rats seems to be secondary to an increased transport of plasma L-Trp to their brain. These findings suggest the hypothesis that the mechanism of accelerated synthesis of brain 5-HT in the adult nutritionally recovered animals, may not depended on the increased availability of free plasma L-Trp observed in the undernourished rats, but might be due to a specific change in the TrpOH structure, supported by previous results showing different kinetic and phosphorylating properties. Our observations also suggest that the increased food intake in the recovered animals imply changes in feeding behavior possibly related to the altered serotonin brain neurotransmission.

Serotonergic receptors in the brain of in utero undernourished rats

“…This study confirmed that early undernourishment produces a marked deficit in physical growth (Anugwa and Pond, 1989;Fernandez et al, 1985;Manjarrez-G et al, 1988Manjarrez-G et al, , 1996 and an elevation of 5-HT synthesis rate in the brain- stem and in the cerebral cortex, that is known to be secondary to an activation of the whole serotonin metabolic path, since the fetal period (Hernandez-R, 1979(Hernandez-R, , 1980Hernandez-R et al, 1989;Manjarrez-G et al, 1988Manjarrez-G et al, , 1994Manjarrez-G et al, , 1998Manjarrez-G et al, , 1999.…”

Serotonin and dopamine in the hypothalamus of control and malnourished mother rats during pregnancy and lactation and body composition of their offspring

“…25 This interaction may determine the individual's nutritional status in adulthood and a predisposition to obesity, probably related to changes in eating behavior as a consequence of a brain serotonin disorder during fetal and adult life. 13,26 Furthermore, these biochemical results confirm that the metabolic alterations already reported 12,13 in the brain serotonergic system are also present in undernourished mothers during pregnancy and lactation, in this case at the hypothalamic level, secondary to an increase of the free fraction of plasma L-Trp. It was also observed that the concentration of dopamine in the hypothalamus of these undernourished mothers decreased significantly compared to control mothers.…”

“…Up to day 21 these pups showed a tendency to develop long-lasting overweight as confirmed in an earlier study. 13 In conclusion, the present results show that serotonin and dopamine at the hypothalamic level are actively involved in the release of PRL and breast milk production. The results also support the fact that ad libitum feeding in malnourished animals from birth is the main factor involved in nutritional recovery and may predispose to obesity in adulthood.…”

“…12,13 However, when these in utero malnourished offspring were subjected to a regimen of nutritional rehabilitation from birth, they had a return to normal physical growth and body composition due to a higher amount of total lipids and proteins. These observations allow us to suggest that when food restriction is eliminated during prenatal or early neonatal life, cells involved in the growth process can continue with their genetically programmed development, if and when nutrition and endocrine medium is optimized, thus permitting a complete nutritional recovery.…”

“…11 Furthermore, it has been observed that when the in utero malnourished offspring are suckled by normal mothers, they recover their physical and biochemical growth and there is a predisposition for the development of obesity during adulthood. 12,13 Therefore, in order to obtain more information and to further clarify the physiological processes involved in lactation in normal controls and malnourished subjects, the aim of the present study was to determine the concentration of dopamine and serotonin in the hypothalamus and to assess the characteristics of milk and the body composition of the offspring.…”