Increased expression of Hes5 protein in Notch signaling pathway in the hippocampus of mice offspring of dams fed a high‐fat diet during pregnancy and suckling

Abstract

Maternal high-fat diet (HFD) impairs hippocampal development of offspring promoting decreased proliferation of neural progenitors, in neuronal differentiation, in dendritic spine density and synaptic plasticity reducing neurogenic capacity. Notch signaling pathway participates in molecular mechanisms of the neurogenesis. The activation of Notch signaling leads to the upregulation of Hes5, which inhibits the proliferation and differentiation of neural progenitors. This study aimed to investigate the Notch/Hes pathway activation in the hippocampus of the offspring of dams fed an HFD. Female Swiss mice were fed a control diet (CD) and an HFD from pre-mating until suckling. The bodyweight and mass of adipose tissue in the mothers and pups were also measured. The mRNA and protein expression of Notch1, Hes5, Mash1, and Delta1 in the hippocampus was assessed by RT-PCR and western blotting, respectively. Dams fed the HFD and their pups had an increased bodyweight and amount of adipose tissue. Furthermore, the offspring of mothers fed the HFD exhibited an increased Hes5 expression in the hippocampus compared with CD offspring. In addition, HFD offspring also expressed increased amounts of Notch1 and Hes5 mRNA, whereas Mash1 expression was decreased. However, the expression of Delta1 did not change significantly. We propose that the overexpression of Hes5, a Notch effector, downregulates the expression of the proneural gene Mash1 in the offspring of obese mothers, delaying cellular differentiation. These results provide further evidence that an offspring's hippocampus is molecularly susceptible to maternal HFD and suggest that Notch1 signaling in this brain region is important for neuronal differentiation.

Maternal high-fat diet influences stroke outcome in adult rat offspring

“…Moreover, consistent with previous studies (Molteni et al 2002, Wu et al 2004, we also found that HFD consumption in adulthood decreases the hippocampal BDNF levels. Additionally, maternal HFD has also been demonstrated to impair hippocampal development of offspring, promoting decreased neuronal differentiation, and Notch 1 signaling in this brain region may be involved in the process (Mendes-da-Silva et al 2015). Glucocorticoid exposure is a critical determinant of stroke outcome.…”

Maternal High-Fat Diet Modifies the Immature Hippocampus Vulnerability to Perinatal Asphyxia in Rats

“…One of the most vulnerable brain areas affected by HFD is the hippocampus, resulting in a delayed utero development [5], learning and memory impairment, and addiction-like behaviors [6]. The mechanisms involved are exacerbated proliferation of astrocytes, increased stress response to acute stimuli [7], and altered development of the placental vasculature [8].…”

Maternal high-fat diet acts as a stressor increasing maternal glucocorticoids’ signaling to the fetus and disrupting maternal behavior and brain activation in C57BL/6J mice

“…In this context, leptin is a main player known to be involved in the regulation of body weight and energy balance by acting as a hunger suppressant signal to the brain (Hamed et al, 2011). According to a recent experimental study maternal HFD might also result in hippocampal inflammation with several consequences on the offspring, given the pivotal role played by the hippocampus in several cognitive processes, in addition to emotional behavior (Mendes-da-Silva et al, 2015).…”