Maternal High-Energy Diet during Pregnancy and Lactation Impairs Neurogenesis and Alters the Behavior of Adult Offspring in a Phenotype-Dependent Manner

Abstract

Obesity is one of the biggest and most costly health challenges the modern world encounters. Substantial evidence suggests that the risk of metabolic syndrome or obesity formation may be affected at a very early stage of development, in particular through fetal and/or neonatal overfeeding. Outcomes from epidemiological studies indicate that maternal nutrition during pregnancy and lactation has a profound impact on adult neurogenesis in the offspring. In the present study, an intergenerational dietary model employing overfeeding of experimental mice during prenatal and early postnatal development was applied to acquire mice with various body conditions. We investigated the impact of the maternal high-energy diet during pregnancy and lactation on adult neurogenesis in the olfactory neurogenic region involving the subventricular zone (SVZ) and the rostral migratory stream (RMS) and some behavioral tasks including memory, anxiety and nociception. Our findings show that a maternal high-energy diet administered during pregnancy and lactation modifies proliferation and differentiation, and induced degeneration of cells in the SVZ/RMS of offspring, but only in mice where extreme phenotype, such as significant overweight/adiposity or obesity is manifested. Thereafter, a maternal high-energy diet enhances anxiety-related behavior in offspring regardless of its body condition and impairs learning and memory in offspring with an extreme phenotype.

Multi-Omics Data Integration Reveals Sex-Dependent Hippocampal Programming by Maternal High-Fat Diet during Lactation in Adult Mouse Offspring

“…In this sense, it has also been shown that the increase in AHN by physical exercise [81] or in transgenic mouse models [82] reduces age-related cognitive decline. In addition, studies indicate that a maternal HF during the perinatal period decreases cell proliferation and differentiation during AHN, altering memory [83,84]. However, other studies agree with our results, showing an increase in the number of stem cells and newly formed neurons in offspring whose mothers were fed a HF.…”

Adult rats sired by obese fathers present learning deficits associated with epigenetic and neurochemical alterations linked to impaired brain glutamatergic signaling

“…Similarly, animal studies have shown that the offspring born to obese dams display reduced working, spatial, and associative memory 14–17 . Several mechanisms have been proposed to underpin the cognitive deficits in the offspring of obese mothers including impaired expression of BDNF and reduced neurogenesis and dendritic arborisation in the hippocampus 18–21 …”

“…[14][15][16][17] Several mechanisms have been proposed to underpin the cognitive deficits in the offspring of obese mothers including impaired expression of BDNF and reduced neurogenesis and dendritic arborisation in the hippocampus. [18][19][20][21] There is also a large body of evidence demonstrating that paternal obesity predisposes the offspring to metabolic diseases. [22][23][24][25] However, whether brain function can be affected by the obese state of the father, has been barely examined.…”

Early Intervention of Elateriospermum tapos Yoghurt in Obese Dams Mitigates Intergenerational Cognitive Deficits and Thigmotactic Behaviour in Male Offspring via the Modulation of Metabolic Profile

“…In animal studies, maternal consumption of an HFD during pregnancy and lactation has been shown to impair cognitive function in offspring. These offspring exhibit deficits in learning and memory tasks, as well as increased anxiety-like behaviour [ 10 ]. Various mechanisms have been identified to cause cognitive decline in the offspring of maternal subjects that consume an HFD during pregnancy and lactation.…”