title: Early malnutrition results in long-lasting impairments in pattern-separation for overlapping novel object and novel location memories and reduced hippocampal neurogenesis.
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.
authors.affiliation: INRA, UMR1280 Physiologie des Adaptations Nutritionnelles, Université de Nantes, Nantes Atlantique Université, 44096, Nantes, France.
authors.forename: Georgina
authors.initials: G
authors.lastname: Pérez-García
authors.affiliation: INRA, UMR1280 Physiologie des Adaptations Nutritionnelles, Université de Nantes, Nantes Atlantique Université, 44096, Nantes, France.
authors.forename: Omar
authors.initials: O
authors.lastname: Guzmán-Quevedo
authors.affiliation: INRA, UMR1280 Physiologie des Adaptations Nutritionnelles, Université de Nantes, Nantes Atlantique Université, 44096, Nantes, France.
authors.forename: Raquel
authors.initials: R
authors.lastname: Da Silva Aragão
authors.affiliation: INRA, UMR1280 Physiologie des Adaptations Nutritionnelles, Université de Nantes, Nantes Atlantique Université, 44096, Nantes, France.
authors.forename: Francisco
authors.initials: F
authors.lastname: Bolaños-Jiménez
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D003072:Cognition Disorders / Q000209:etiology* / Q000503:physiopathology*; D018753:Diet, Protein-Restricted / Q000009:adverse effects; D004195:Disease Models, Animal; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006624:Hippocampus / Q000502:physiology*; D007859:Learning Disabilities / Q000209:etiology / Q000503:physiopathology; D008297:Male; D044342:Malnutrition / Q000150:complications*; D008568:Memory; D055495:Neurogenesis; D051381:Rats
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; C019277:brain-derived growth factor