High‐Salt Exposure During Perinatal Development Enhances Stress Sensitivity

Abstract

Excess consumption of dietary sodium during pregnancy has been shown to impair offspring cardiovascular function and enhance salt preference in adulthood, but little is known regarding the long-term impact of this nutritional surplus on offspring brain morphology and behavior. Using a combination of cellular and behavioral approaches, we examined the impact of maternal salt intake during the perinatal period on structural plasticity in the prefrontal cortex (PFC) and nucleus accumbens (NAc) in weanling and adult offspring as well as reward- and stress-driven behaviors in adult offspring. We found that weanling rats born to 4% NaCl-fed dams exhibited an increase and decrease in thin spine density in the infralimbic PFC (IL-PFC) and prelimbic PFC (PL-PFC), respectively, as well as an increase in mushroom spine density in the NAc shell, compared to 1% NaCl-fed controls. Structural changes in the IL-PFC and NAc shell persisted into adulthood, the latter of which is a phenotype that has been observed in rats exposed to early life stress. There was no effect of maternal salt intake on reward-driven behaviors, including sucrose preference, conditioned place preference (CPP) for cocaine, and forced swim stress (FSS)-induced reinstatement of cocaine-induced CPP. However, rats born to high-salt fed dams spent less time swimming in the FSS and displayed heightened plasma CORT levels in response to the FSS compared to controls, suggesting that early salt exposure increases stress sensitivity. Overall, our results suggest that perinatal salt exposure evokes lasting impacts on offspring physiology and behavior.

High-Salt Diet in the Pre- and Postweaning Periods Leads to Amygdala Oxidative Stress and Changes in Locomotion and Anxiety-Like Behaviors of Male Wistar Rats

“…In turn, this can lead to the release of inflammatory signals, resulting in neuroinflammation, loss of function, and, consequently, in behavioral changes (Hatanaka et al, 2016;Cirulli et al, 2020;Dias et al, 2020;Maciel August et al, 2020). Previous studies in rodents have shown that HS diets caused an imbalance in the brain redox state, with decreased cognition (Liu et al, 2014;Ge et al, 2017;Faraco et al, 2019) and increased reactivity to stressful situations (Bai et al, 2017;Dingess et al, 2018). Moreover, a HS diet in the preconception, gestation, and lactation periods has been shown to negatively influence the redox state of the cerebellum, hypothalamus, and hippocampus of the offspring (Stocher et al, 2018).…”

“…Studies in rodents that used dietary or water salt supplementation (2–8%) confirm these findings, reporting impaired cognition, aggravation of cerebral ischemic injury, and high-stress responsivity ( Ge et al, 2017 ; Faraco et al, 2018 , 2019 ; Mitchell et al, 2018 ; Gilman et al, 2019a ; Zhang et al, 2020 ). Importantly, preclinical studies suggest that the maternal high-salt diet can also induce changes in locomotion, inhibition, and anxiety in the offspring, when fed in the preconception, gestation, or lactation periods ( Mcbride et al, 2008 ; Mecawi and Almeida, 2017 ; Dingess et al, 2018 ). During these periods, the offspring is highly susceptible to dietary salt, which may impact on development, potentially leading to lifelong changes in metabolism and behavior.…”

Mechanisms Underlying the Cognitive and Behavioural Effects of Maternal Obesity

“…By contrast, preclinical studies using affective measures in rodents show mixed results, with maternal obesity found to increase [ 26 , 30 , 31 , 39 , 41 , 53 ] or decrease anxiety -like behaviour [ 27 , 38 , 43 , 49 ]. The age at which behaviour was measured may impact on these findings.…”

Habitual salt preference worsens blood pressure in hospitalized hypertensive patients with omicron infection under epidemic-related stress

“…Experimental studies have suggested that early high salt exposure may increase stress sensitivity, involving changes to the structural plasticity of the prefrontal cortex (PFC) and nucleus accumbens (NAc) [ 13 ]. Both the PFC and NAc have been found to be involved in reward processing [ 37 ], and our previous work found that those areas also participated in high SP [ 22 , 24 ].…”

“…High salt intake is an important risk factor associated with elevated BP and is related to psychological stress. Experimental studies have found that early high salt exposure may increase the risk of stress-related neuropsychiatric disorders and stress sensitivity [ 13 , 14 ]. In the USA, a significant increase in BP was observed during and after the COVID-19-related lockdown [ 15 ], which was explained by the authors as partially due to the emotional stress of the lockdown.…”