NURTIENT RESTRICTION: FETAL BABOON BRIAN DEVELOPMENT

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Introduction The vast majority of brain insulin-like growth factor (IGF) studies have been done in rodent models. However, the fact that much of brain development that goes on during gestation (G) in primates occurs postnatally in laboratory rodents is a clear disadvantage in rodent models [1]. In addition, it is important to emphasize a point made by Rice and Barone that"... both the visual and auditory systems of albino animals of all species are abnormal; therefore, albino rats or mice are a poor choice for assessment when the nervous system is of interest." [2]. This very important caveat makes it imperative that observations made in rats be confirmed in a primate model prior to assuming applicability to humans. The present application looks at the effects of 30% maternal (M) nutrient restriction (NR) on fetal brain development in a primate model, the baboon. The paradigm does not produce weight loss in the fetus; however as will be shown, it does produce dramatic reductions in many parameters in the developing brain. In addition, our 30% MNR paradigm reduces fetal blood urea nitrogen thus suggesting fetal NR and demonstrating that body weight is a very poor indicator of fetal NR. We have chosen to look at the frontal cortex since it is an area of the brain that has been shown in rodent models to be adversely affected by even relatively mild (isocaloric, two thirds less protein) nutrient restriction [3] and we wish to determine if a similar result will be seen in a primate model. In addition, we believe that NR effects in this area will be mirrored by detriments in other areas such as the cerebellum and accordingly, we will retain other brain areas for future studies. Investigations of this type cannot ethically be done in humans; this fact makes studies in a model with a brain that is similar to humans such as the baboon, all the more urgent. Without knowledge in this area, diagnostic procedures and therapies for deficits cannot be designed and strategies for pro-active interventions cannot be planned.