Abstract
Numerous epidemiological studies indicate that malnutrition during in utero development and/or childhood induces long-lasting learning disabilities and enhanced susceptibility to develop psychiatric disorders. However, animal studies aimed to address this question have yielded inconsistent results due to the use of learning tasks involving negative or positive reinforces that interfere with the enduring changes in emotional reactivity and motivation produced by in utero and neonatal malnutrition. Consequently, the mechanisms underlying the learning deficits associated with malnutrition in early life remain unknown. Here we implemented a behavioural paradigm based on the combination of the novel object recognition and the novel object location tasks to define the impact of early protein-restriction on the behavioural, cellular and molecular basis of memory processing. Adult rats born to dams fed a low-protein diet during pregnancy and lactation, exhibited impaired encoding and consolidation of memory resulting from impaired pattern separation. This learning deficit was associated with reduced production of newly born hippocampal neurons and down regulation of BDNF gene expression. These data sustain the existence of a causal relationship between early malnutrition and impaired learning in adulthood and show that decreased adult neurogenesis is associated to the cognitive deficits induced by childhood exposure to poor nutrition.
Highlights
Capacities have been reported in early malnourished rats
We implemented a learning paradigm based on the combination of the Novel Object Recognition (NOR) and the Novel Object Location (NOL) tasks to define the impact of early protein-restriction on memory formation and consolidation and to investigate the cellular and molecular mechanisms underpinning the learning disabilities of early malnourished individuals
If the two objects initially explored are presented during the test session, but with one of the objects placed at a different spatial location that during training, the displaced familiar object is explored to the same extent as a novel object[30], providing a measure of spatial memory
Summary
Capacities have been reported in early malnourished rats. These latter conflicting results might be explained by the differences in the type and severity of the nutritional insult[4]. We implemented a learning paradigm based on the combination of the Novel Object Recognition (NOR) and the Novel Object Location (NOL) tasks to define the impact of early protein-restriction on memory formation and consolidation and to investigate the cellular and molecular mechanisms underpinning the learning disabilities of early malnourished individuals These tests relay on the animal’s innate preference for novelty such that learning is not driven by external positive or negative motivational factors, like food reward or stressful and painful stimuli, avoiding bias in the interpretation of behavioural results associated with the effects of malnutrition on feeding and significantly limiting confounding biases due to impaired emotional reactivity
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