Prenatal Protein Malnutrition Produces Resistance to Distraction Similar to Noradrenergic Deafferentation of the Prelimbic Cortex in a Sustained Attention Task.

Lori A Newman,Arielle G Rabinowitz,Jaime Baraiolo,Janina R Galler,David J Mokler,Jill A Mcgaughy

doi:10.3389/fnins.2019.00123

Abstract

Exposure to malnutrition early in development increases likelihood of neuropsychiatric disorders, affective processing disorders, and attentional problems later in life. Many of these impairments are hypothesized to arise from impaired development of the prefrontal cortex. The current experiments examine the impact of prenatal malnutrition on the noradrenergic and cholinergic axons in the prefrontal cortex to determine if these changes contribute to the attentional deficits seen in prenatal protein malnourished rats (6% casein vs. 25% casein). Because prenatally malnourished animals had significant decreases in noradrenergic fibers in the prelimbic cortex with spared innervation in the anterior cingulate cortex and showed no changes in acetylcholine innervation of the prefrontal cortex, we compared deficits produced by malnutrition to those produced in adult rats by noradrenergic lesions of the prelimbic cortex. All animals were able to perform the baseline sustained attention task accurately. However, with the addition of visual distractors to the sustained attention task, animals that were prenatally malnourished and those that were noradrenergically lesioned showed cognitive rigidity, i.e., were less distractible than control animals. All groups showed similar changes in behavior when exposed to withholding reinforcement, suggesting specific attentional impairments rather than global difficulties in understanding response rules, bottom-up perceptual problems, or cognitive impairments secondary to dysfunction in sensitivity to reinforcement contingencies. These data suggest that prenatal protein malnutrition leads to deficits in noradrenergic innervation of the prelimbic cortex associated with cognitive rigidity.

Highlights

Malnutrition impacts approximately one in four children worldwide (WHO, 2012)
Prenatal Protein Malnutrition Prenatal protein malnutrition resulted in significantly fewer DBH positive axons in the prelimbic cortex (PL) relative to control values [F(1,24) = 5.61, p = 0.03; Figures 1A,B, 2A] but did not alter axon density in anterior cingulate cortex (ACC) [F(1,24) = 0.26, p = 0.61; Figure 2A]
Few studies have assessed the effects of noradrenergic damage on sustained attention in the rat, and published results have been inconclusive

Summary

Introduction

Malnutrition impacts approximately one in four children worldwide (WHO, 2012). Longitudinal studies of adults with exposure to prenatal food restriction during the Dutch famine and the Chinese famine of 1959–1961 Consistent and compelling data from human studies are often complicated by a multitude of other factors that coincide with childhood malnutrition, e.g., poverty, infection, stress, and maternal depression (Salt et al, 1988; Galler et al, 2000; Walker et al, 2011) While these long-term effects are hypothesized to result from dysregulation of the prefrontal cortex, it is difficult to ascertain the relationship between prenatal malnutrition and the prefrontal cortex in human studies. Animal models have shown impaired attentional processing as a result of prenatal iron deficiency (Mohamed et al, 2011), vitamin D (Turner et al, 2013), and protein levels (McGaughy et al, 2014). These nutritional deficits are known to impair prefrontal circuits hypothesized to be critical to attention (Groves et al, 2013; Grissom et al, 2014; McGaughy et al, 2014)

Objectives

Methods

Results

Conclusion