Sucrose Consumption Alters Serotonin/Glutamate Co-localisation Within the Prefrontal Cortex and Hippocampus of Mice

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.

Neural serotonergic circuits for controlling long-term voluntary alcohol consumption in mice

“…4A–C ) and quantified (Fig. 4D–F ) as previously described [ 46 , 47 , 54 , 55 ]. The volume of 5-HT varicosities (boutons) in the DG, CA3 and LS was quantified in water-exposed animals (Water), ethanol-exposed animals chronically treated (2 weeks, following 12 weeks of consumption) with either vehicle (EtOH + veh) or with the 5-HT 1A receptor partial agonist, tandospirone at 3 mg/kg/day, i.p.…”

“…Sections were rinsed in PBST (0.1 M PBS, 0.3% Triton-X100, 0.03% Tween-20), and incubated in Streptavidin-Alexa 488 (Thermofisher, S11223, 1:1000) diluted in PBST, at room temperature for 30 min, rinsed 3 × 5 min in PBST, incubated in DAPI diluted in PBS (Thermofisher, #D1306, 1:1000), rinsed 3 × 5 min in PBS and mounted on slide with Prolong Gold antifade (Thermofisher, #P10144). For 5-HT innervation, immunohistochemistry was performed by a blind experimenter as previously described [ 46 , 47 ]. Briefly, after permeabilization and blocking as above, sections were incubated with rat anti-5-HT antibody (Merck Millipore MAB352, 1:100) for 72 h at room temperature, followed by goat anti-rat biotinylated secondary antibody (Jackson Immunoresearch # 112-065-003, 1:200) for 4 h, and 30 min incubation with streptavidin-Cy3 (Thermofisher, #434315, 1:1000).…”

A High-Sugar Diet Consumption, Metabolism and Health Impacts with a Focus on the Development of Substance Use Disorder: A Narrative Review

“…In addition to sucrose, previous studies have demonstrated similarities following acute exposure to another non-caloric sweetener saccharin at the level of the NAc [ 134 , 135 , 136 ]. Very recent study indicated that chronic (12 weeks) 5% sucrose consumption to mice resulted in a reduction in the serotonin (5-HT) receptors innervation within the PFC and dentate gyrus of the hippocampus, a reduction in the number of microglia in the latter brain structure as well as a decrease in the density of the vesicular glutamate transporter (VGLUT3) and of 5-HT/VGUT3 varicosities but not in the number of oligodendrocyte progenitor cells [ 137 ].…”

“…Hippocampus-dependent alteration in behaviours was accompanied with altered hippocampal neurogenesis such as a reduction in the proliferation and differentiation of newborn neurons in the dentate gyrus [ 141 ], which raises a positive correlation between high- and long-term exposure to sucrose during adolescent and neurocognitive defects in adulthood. Furthermore, anxiety-like or depressive-like symptoms being observed simultaneously following long-term 8–25% sucrose consumption [ 123 , 143 , 144 , 145 , 146 , 147 , 148 , 149 ], but not with 5% sucrose consumption [ 137 ]. In addition, a high sucrose intake (30% wt/vol) in pregnant mice induced behavioural phenotypes similar to ADHD in the offspring, manifested by increased motor activity, and impulsivity.…”

A New Player in the Hippocampus: A Review on VGLUT3+ Neurons and Their Role in the Regulation of Hippocampal Activity and Behaviour

“…In relation to emotions , changes in sucrose intake in rodents are known to reflect depressive-like behaviour [ 149 , 150 ]. In this respect, chronic sucrose consumption decreased the number of VGLUT3+ varicosities in the dentate gyrus of the mouse hippocampus independently from their 5-HT marker expression [ 151 ]. Interestingly, in rats, repeated sucrose consumption increased VGLUT3 expression in the nucleus accumbens, the centre known for reward, as well [ 152 ].…”