Early-life environmental insults have been shown to promote long-term development of chronic non-communicable diseases, including metabolic disturbances and mental illnesses. As such, premature consumption of high-sugar foods has been associated to early onset of detrimental outcomes, whereas underlying mechanisms are still poorly understood. In the present study, we sought to investigate whether early and sustained exposure to high-sucrose diet promotes metabolic disturbances that ultimately might anticipate neurological injuries. At postnatal day 21, weaned male rats started to be fed a standard chow (10 % sucrose, CTR) or a high-sucrose diet (25 % sucrose, HSD) for 9 weeks prior to euthanasia at postnatal day 90. HSD did not alter weight gain and feed efficiency between groups, but increased visceral, non-visceral and brown adipose tissue accumulation. HSD rats demonstrated elevated blood glucose levels in both fasting and fed states, which were associated to impaired glucose tolerance. Peripheral insulin sensitivity did not change, whereas hepatic insulin resistance was supported by increased serum triglyceride levels, as well as higher TyG index values. Assessment of hippocampal gene expression showed endoplasmic reticulum (ER) stress pathways were activated in HSD rats, as compared to CTR. HSD rats had overexpression of unfolded protein response sensors, PERK and ATF6; ER chaperone, PDIA2 and apoptosis-related genes, CHOP and Caspase 3; but decreased expression of chaperone GRP78. Finally, HSD rats demonstrated impaired neuromuscular function and anxious behavior, but preserved cognitive parameters. In conclusion, our data indicate that early exposure to HSD promote metabolic disturbances, which disrupt hippocampus homeostasis and might precociously affect its neurobehavioral functions.
Background. Reperfusion syndrome after carotid endarterectomy is a complication associated with cerebrovascular self-regulation in a chronically hypoperfused cerebral hemisphere, leading to severe neurological damage. Vitamin C is an important antioxidant in brain metabolism that has shown some neuroprotective actions. Objective. To investigate the potential effects of vitamin C on cerebral reperfusion in comparison with placebo (saline) in rats. Methods. Male Wistar rats were divided into 3 groups: (i) Sham (n=4), animals exposed to carotid arteries dissection without clamping; (ii) Control (n=4), animals that received an intraperitoneal injection of 0.9% saline solution (0.1 mL/kg) and underwent carotid arteries dissection with temporary clamping; (iii) Vitamin C (n=4), animals that received an intraperitoneal injection of vitamin C (750 mg/kg) and underwent carotid arteries dissection with temporary clamping. Behavioral assessment was then performed in all groups, which included the open field, Morris water maze and rotarod tests. Levels of malondialdehyde (MDA) in the hippocampus and striatum were measured using a fluorometric assay. Results. Rats treated with vitamin C presented with a similar behavior as compared to the Sham group in all the three tests (p>0.05), but it was significantly different from controls (p<0.05). Vitamin C was also found to reduce MDA levels in both hippocampus and striatum when compared to placebo (p<0.05). Conclusion. In the present study, vitamin C was associated with behavioral and motor preservation as well as decreased cerebral MDA levels after induced cerebral ischemia in rats.
BackgroundMetabolic syndrome (MS)‐related conditions promotes endoplasmic reticulum stress (ERS) in order to control their deleterious effects through activation of adaptive responses known as Unfolded Protein Response (UPR). However, under chronic stress, UPR can evolve to apoptotic pathways. Previously, we have shown that MS induced by high‐sucrose diet triggers the ERS and apoptotic pathways in hippocampus and lead to motor and behavioral impairments in young rats.AimsIn the present study we sought to investigate if sustained exposure to such diet is capable to intensify those metabolic disturbances and anticipate neurological impairments in adult rats.MethodsThus, weaned Wistar rats were divided in two groups: the control group (CTR, n=7), fed with a standard chow; and obese group (HSD, n=7), fed with high‐sucrose diet (25% sucrose). Both groups were followed for 6 months and evaluated for MS development; serum redox profile; and hippocampal gene and protein expressions of UPR sensors (IRE1α, PERK and ATF6), chaperones (GRP78, GRP94, PDI, calnexin and calreticulin), neural plasticity marker (BDNF), antioxidant defense (NRF2), senescence (P53 and P21) and apoptosis (BCL2, CHOP and PARP‐1). Furthermore, cognitive, behavioral and motor functions were also assessed, through Morris water maze, open field and rotarod test, respectively. For aging control, 20 month‐old rats (OLD, n=7) fed with standard chow were included as an aging control for gene/protein expressions and neurological assessments.ResultsThe exposure to high‐sucrose diet was capable to induce MS with marked weight gain, central obesity, dysglicemia in both fasting and fed states, hypertriglyceridemia and high free fatty acids, fat storage in liver, glucose intolerance, hyperinsulinemia and peripheral as well as hepatic insulin resistance. The redox profile assessment showed higher lipid peroxidation with increased serum MDA levels and higher SOD activity in HSD as compared to CTR, but catalase was unchanged. UPR sensors gene expression was reduced in both HSD and OLD groups. All chaperones evaluated presented decreased gene expression, but only GRP78 and GRP94 also presented a decreased protein expression. BDNF expression was reduced in HSD (FC 0.3) and OLD groups, but NRF2 did not present any difference. As expected, the senescence markers were increased in OLD group, but only P21 was increased in HSD (FC 1.8). Assessment of apoptotic pathways showed decreased expression of BCL2 and increased gene and protein expression of CHOP. Assessment of PARP‐1 protein expression suggested the presence of calpain, a necrosis marker. Neurological evaluation demonstrated motor deficit, anxiogenic behavior and cognitive impairments (learning and spatial memory) in HSD.ConclusionsIn to to, our data support that sustained exposure to high‐sucrose diet promotes metabolic disturbances, which disrupt hippocampus homeostasis and lead to cognitive and motor impairments in 6‐months old rats.Support or Funding InformationFundação de Amparo à Pesquisa e ao Desenvolvimento Científico e Tecnológico do Maranhão – FAPEMA and rede INCT Redoxoma
Metabolic dysfunctions, such as hyperglycemia and insulin resistance, have been associated to cognitive impairment and dementia regardless of advanced age, although the underlying mechanisms are still elusive. Thus, this study investigates the deleterious effects of metabolic syndrome (MetS) induced by long-term exposure to a high-sucrose diet on motor and cognitive functions of male adult rats and its relationship with hippocampal endoplasmic reticulum (ER) stress. Weaned Wistar male rats were fed a high-sucrose diet until adulthood (HSD; 6 months old) and compared to both age-matched (CTR; 6 months old) and middle-aged chow-fed rats (OLD; 20 months old). MetS development, serum redox profile, behavioral, motor, and cognitive functions, and hippocampal gene/protein expressions for ER stress pro-adaptive and pro-apoptotic pathways, as well as senescence markers were assessed. Prolonged exposure to HSD induced MetS hallmarked by body weight gain associated to central obesity, hypertriglyceridemia, insulin resistance, and oxidative stress. Furthermore, HSD rats showed motor and cognitive decline similar to that in OLD animals. Noteworthy, HSD rats presented marked hippocampal ER stress characterized by failure of pro-adaptive signaling and increased expression of Chop, p21, and Parp-1 cleavage, markers of cell death and aging. This panorama resembles that found in OLD rats. In toto, our data showed that early and sustained exposure to a high-sucrose diet induced MetS, which subsequently led to hippocampus homeostasis disruption and premature impairment of motor and cognitive functions in adult rats.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.