Abstract
The overconsumption of sugar-sweetened food and beverages underpins the current rise in obesity rates. Sugar overconsumption induces maladaptive neuroplasticity to decrease dietary control. Although serotonin and glutamate co-localisation has been implicated in reward processing, it is still unknown how chronic sucrose consumption changes this transmission in regions associated with executive control over feeding—such as the prefrontal cortex (PFC) and dentate gyrus (DG) of the hippocampus. To address this, a total of 16 C57Bl6 mice received either 5% w/v sucrose or water as a control for 12 weeks using the Drinking-In-The-Dark paradigm (n = 8 mice per group). We then examined the effects of chronic sucrose consumption on the immunological distribution of serotonin (5-HT), vesicular glutamate transporter 3 (VGLUT3) and 5-HT+/VGLUT3+ co-localised axonal varicosities. Sucrose consumption over 12 weeks decreased the number of 5-HT–/VGLUT3+ and 5-HT+/VGLUT3+ varicosities within the PFC and DG. The number of 5-HT+/VGLUT3– varicosities remained unchanged within the PFC but decreased in the DG following sucrose consumption. Given that serotonin mediates DG neurogenesis through microglial migration, the number of microglia within the DG was also assessed in both experimental groups. Sucrose consumption decreased the number of DG microglia. Although the DG and PFC are associated with executive control over rewarding activities and emotional memory formation, we did not detect a subsequent change in DG neurogenesis or anxiety-like behaviour or depressive-like behaviour. Overall, these findings suggest that the chronic consumption of sugar alters serotonergic neuroplasticity within neural circuits responsible for feeding control. Although these alterations alone were not sufficient to induce changes in neurogenesis or behaviour, it is proposed that the sucrose consumption may predispose individuals to these cognitive deficits which ultimately promote further sugar intake.
Highlights
Obesity is an expanding global health issue driven by the overconsumption of high sugar foods (Jacques et al, 2019a)
We found that mice that have chronically consumed sucrose have a decreased number of 5-HT and 5-HT/vesicular glutamate transporter 3 (VGLUT3) varicosities within the prefrontal cortex (PFC) and dentate gyrus (DG)
We found that sucrose consumption decreased the number of microglia within the DG, and increased the number of pMAPK neurons in the PFC
Summary
Obesity is an expanding global health issue driven by the overconsumption of high sugar foods (Jacques et al, 2019a). For sugar to be deemed an addictive substance, the four criteria need to be validated: bingeing, withdrawal, craving and cross-sensitisation. Sugar has been shown to elicit all hallmark signs of addicted behaviours: bingeing, cross-sensitisation (Avena and Hoebel, 2003), tolerance and cravings (Avena et al, 2005). We have previously reported that varenicline, an FDAapproved nicotinic acetylcholine receptor (nAChR) partial agonist significantly reduced long-term 5% binge-like sucrose consumption (Shariff et al, 2016). Chronic long-term 25% sucrose consumption has been recently shown to augment weigh gain, elicit abnormal hyperlocomotion, impair cognitive function and alter neurogenesis (Beecher et al, 2021). Continuous access to 25% sucrose has been investigated in mice, considering the effect of varenicline on 5% sucrose on reducing sugar intake, we had to examine chronic restricted (DID) 5% sucrose consumption
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