Abstract
The corticolimbic circuits in general and the medial prefrontal cortex in particular, undergo maturation during juvenility. It is thus expected that environmental challenges in forms of obesogenic diet can exert different effects in juvenile animals compared to adults. Further, the relationship between glucocorticoids and obesity has also been demonstrated in several studies. As a result, glucocorticoid receptor (GR) antagonists are currently being tested as potential anti-obesity agents. In the present study, we examined the effects of short-term exposure to high-fat diet (HFD) on prefrontal long-term potentiation (LTP) in both juvenile and adult rats, and the role of glucocorticoid receptors (GRs) in modulating these effects. We found HFD impaired prefrontal LTP in both juveniles and adults, but the effects of GR modulation were age- and diet-dependent. Specifically, GR antagonist RU-486 reversed the impairment of LTP in juvenile animals following HFD, and had no effect on control-diet animals. In adult animals, RU-486 has no effect on HFD-impaired LTP, but abolished LTP in control-diet animals. Furthermore, impairments in the prefrontal LTP following HFD are involved with an increase in the mPFC GR levels only in the juveniles. Further, we found that in vivo application of GR agonists into adult mPFC rescued HFD-induced impairment in LTP, suggesting that these receptors might represent strategic therapeutic targets to potentially combat obesity and metabolic related disorder.
Highlights
Overconsumption of a Western diet rich in saturated fat and sugar is recognized as one of the primary risk factors for the development of obesity and associated metabolic disorders (Vickers et al, 2005; Francis and Stevenson, 2013)
We found that brief exposure to high-fat diet (HFD) impaired medial prefrontal cortex (mPFC)-dependent long-term potentiation (LTP) in juveniles and adults; these effects were differently modulated by glucocorticoid receptor (GR) in juveniles and adults
As the GR antagonist modulated prefrontal LTP differently in HFD and chow diet (CD)-fed juveniles and adults, we examined whether these groups differed in GR mRNA expression by using RT-qPCR (Figure 8)
Summary
Overconsumption of a Western diet rich in saturated fat and sugar is recognized as one of the primary risk factors for the development of obesity and associated metabolic disorders (Vickers et al, 2005; Francis and Stevenson, 2013). It has been shown in rats that 6 weeks of HFD or sugar consumption, especially if starting at adolescence (postnatal day; PND 32– 45), has strong adverse effects on prefrontal-dependent cognitive functions (Baker et al, 2014; Reichelt et al, 2015b; Morin et al, 2017; Labouesse et al, 2018). We reported that shortand long-term exposure to HFD during juvenility (PND 27– 29) impaired emotional memory, cognitive functions, long-term potentiation (LTP) in the hippocampus and the amygdala along with dysregulation of the HPA axis (Boitard et al, 2015; Khazen et al, 2019)
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