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.

Environmental enrichment and physical exercise revert behavioral and electrophysiological impairments caused by reduced adult neurogenesis

“…One of the cognitive aspects that were negatively affected after the disruption of adult neurogenesis in the present study was recognition memory, evaluated in the object recognition test (ORT), where the distinction between familiar and unfamiliar object was measured. The ability to discriminate between similar memories such as the recognition of a familiar vs. an unfamiliar object, is the behavioral expression of pattern separation (Pérez‐García et al, ), a term that derives from computational models to map the hippocampal function after presentation of similar patterns to dissimilar representations (Marr, ). Recognition memory correlates to pattern separation as the capacity for separating partially overlapping patterns of activation, allowing the brain to retrieve each as separate from other similar patterns (Holden and Gilbert, ).…”

The involvement of astrocytes in early‐life adversity induced programming of the brain

“…The hippocampus has been extensively studied in this context, because of its key role in cognitive functioning and its high degree of neuronal and synaptic plasticity (Akhondzadeh, ; Lledo, Alonso, & Grubb, ; Malenka, ). There is now ample evidence that ELA in the form of stress or malnutrition leads to impaired cognitive functioning associated with disrupted hippocampal neurogenesis (Abbink, Naninck, Lucassen, & Korosi, ; Lemaire, Koehl, Le Moal, & Abrous, ; Loi, Koricka, Lucassen, & Joels, ; Matos, Orozco‐Solís, de Souza, Manhães‐de‐Castro, & Bolaños‐Jiménez, ; Naninck et al, ; Pérez‐García, Guzmán‐Quevedo, Da Silva Aragão, & Bolaños‐Jiménez, ) and altered synaptic plasticity (Aisa et al, ; Austin, Bronzino, & Morgane, ; Danielewicz, Trenk, & Hess, ; Derks, Krugers, Hoogenraad, Joels, & Sarabdjitsingh, ; for review see Georgieff, Brunette, & Tran, ; J. Yang et al, ). In addition, the involvement of microglia has received some attention (De Luca et al, ; Diz‐Chaves, Pernía, Carrero, & Garcia‐Segura, ; Hoeijmakers et al, ).…”

出生前营养不良致子代易感精神分裂症研究进展

“…低蛋白饲料直至子代出生(PPD模型(prenatal protein deprivation model)) (图1), 发现子代在动物行为、神经 形态学、神经递质和电生理方面都有异常变化, 表现 为学习记忆能力下降 [21] 、前脉冲抑制受损 [22] 、海马 区的齿状回颗粒细胞变小、树突分支降低 [23] . 另外, 这种出生前蛋白质缺乏的大鼠与NMDA受体的结合 增加 [22] , 海马区和前额叶皮层细胞外多巴胺水平显著 降低 [24] .…”