Alterations in behaviour, cerebral cortical morphology and cerebral oxidative stress markers following aspartame ingestion

Onaolapo, Adejoke Yetunde; Onaolapo, Olakunle James; Nwoha, P.U.

doi:10.1016/j.jchemneu.2016.08.006

Cited by 46 publications

(28 citation statements)

References 97 publications

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“…In summary, adulthood hypothalamic gene expression was primarily affected by chronic aspartame exposure and to a lesser extent by developmental NMDAR antagonism. ASP exposure robustly elevated the expression of a network of genes involved in hypothalamic neurosteroidogenesis, together with cell stress and inflammatory genes consistent with previous reports of ASP-induced CNS stress and oxidative damage [ 67 ].…”

Section: Methodssupporting

confidence: 88%

Effect of developmental NMDAR antagonism with CGP 39551 on aspartame-induced hypothalamic and adrenal gene expression

et al. 2018

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RationaleAspartame (L-aspartyl phenylalanine methyl ester) is a non-nutritive sweetener (NNS) approved for use in more than 6000 dietary products and pharmaceuticals consumed by the general public including adults and children, pregnant and nursing mothers. However a recent prospective study reported a doubling of the risk of being overweight amongst 1-year old children whose mothers consumed NNS-sweetened beverages daily during pregnancy. We have previously shown that chronic aspartame (ASP) exposure commencing in utero may detrimentally affect adulthood adiposity status, glucose metabolism and aspects of behavior and spatial cognition, and that this can be modulated by developmental N-methyl-D-aspartate receptor (NMDAR) blockade with the competitive antagonist CGP 39551 (CGP). Since glucose homeostasis and certain aspects of behavior and locomotion are regulated in part by the NMDAR-rich hypothalamus, which is part of the hypothalamic-pituitary-adrenal- (HPA) axis, we have elected to examine changes in hypothalamic and adrenal gene expression in response to ASP exposure in the presence or absence of developmental NMDAR antagonism with CGP, using Affymetrix microarray analysis.ResultsUsing 2-factor ANOVA we identified 189 ASP-responsive differentially expressed genes (DEGs) in the adult male hypothalamus and 2188 in the adrenals, and a further 23 hypothalamic and 232 adrenal genes significantly regulated by developmental treatment with CGP alone. ASP exposure robustly elevated the expression of a network of genes involved in hypothalamic neurosteroidogenesis, together with cell stress and inflammatory genes, consistent with previous reports of aspartame-induced CNS stress and oxidative damage. These genes were not differentially expressed in ASP mice with CGP antagonism. In the adrenal glands of ASP-exposed mice, GABA and Glutamate receptor subunit genes were amongst those most highly upregulated. Developmental NMDAR antagonism alone had less effect on adulthood gene expression and affected mainly hypothalamic neurogenesis and adrenal steroid metabolism. Combined ASP + CGP treatment mainly upregulated genes involved in adrenal drug and cholesterol metabolism.ConclusionASP exposure increased the expression of functional networks of genes involved in hypothalamic neurosteroidogenesis and adrenal catecholamine synthesis, patterns of expression which were not present in ASP-exposed mice with developmental NMDAR antagonism.

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Section: Methodssupporting

confidence: 88%

Effect of developmental NMDAR antagonism with CGP 39551 on aspartame-induced hypothalamic and adrenal gene expression

et al. 2018

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“…Astrocytes increase GFAP expression progressively during neuronal damage; therefore, it is widely accepted that GFAP reactivity can be used as a sensitive and reliable marker for neurological insults . As shown previously, chronic administration of mice with increasing doses of aspartame can induce cerebral oxidative stress, histomorphological changes (loss of normal cortex architecture), and GFAP‐reactivity in cerebral cortex as well as behavioral alterations . Also, chronic aspartame treatment may cause dose‐related loss of hippocampal neuronal cells, increase in glial cell density, and spatial‐memory deficit in mice .…”

Section: Discussionmentioning

confidence: 81%

Evaluation of long‐term effects of artificial sweeteners on rat brain: a biochemical, behavioral, and histological study

Erbaş

Erdoğan

Khalilnezhad

et al. 2018

J Biochem & Molecular Tox

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The aim of the present study was to compare the effects of artificial sweeteners (aspartame, saccharin, and sucralose) on rat brain. Twenty-four adult male Sprague-Dawley rats were included in the study. The control group (n = 6) received regular tap water, whereas other groups received aspartame (3 mg/kg/day, n = 6,) or saccharin (3 mg/kg/day, n = 6) or sucralose (1.5 mg/kg/day, n = 6) in the drinking water. Following 6 weeks, the passive avoidance learning (PAL) test was performed to evaluate the neurobehavioral effects of sweeteners. The brains were assessed for lipid peroxides, neuron count, and Glial fibrillary acidic protein (GFAP) immunohistochemistry. Our results demonstrated that chronic intake of sweeteners significantly impaired PAL performance in all groups. Hippocampal CA1-CA3 areas revealed significantly lower neuronal count in aspartame and increased GFAP expression in all groups. Brain lipid peroxides were significantly higher in all groups. Our findings suggest that long-term consumption of artificial sweeteners may have harmful effects on cognition and hippocampal integrity in rats.

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“…Sections of the cerebral cortex and hippocampus were processed for paraffin-embedding, cut at 5 µm and stained with haematoxylin and eosin for general histological study as previously described [ 11 , 19 , 20 ].…”

Section: Methodsmentioning

confidence: 99%

An Assessment of the Effects of Azodicarbonamide-containing Diet on Neurobehaviour, Brain Antioxidant Status and Membrane Lipid Peroxidation Status in Rats

Olofinnade

Adeyeba

Onaolapo

et al. 2020

CNSAMC

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Background: Azodicarbonamide is a dough-enhancer used in the process of breadmaking in countries like Nigeria. While there have been suggestions that it is a sensitizer of the respiratory system, there is a dearth of information on its effects on the central nervous system. Aim: This study assessed the effects of azodicarbonamide on the central nervous system (ADA) in rats. Objective: The effects of ADA-containing diet on neurobehaviour, brain antioxidant status, and neuromorphology of selected brain regions in rats were examined. Method: Forty adult rats were randomly-assigned into four groups of ten rats each, and were given standard diet or diet containing ADA at 1, 2 and 4% respectively. Rats were fed a standard diet or ADA-containing diet for a period of 28 days. Weekly body weight assessment and daily estimation of food intake were done. Behavioural tests in the Open field, Y-maze, radial-arm maze, and Elevated Plus Maze (EPM) were conducted on day 29. Twenty-four hours after the last behavioural test, animals were euthanised, whole brains were dissected, weighed, and either homogenised for assessment of lipid peroxidation and antioxidant status; or sectioned and processed for general histology. Results : Consumption of ADA-containing diet was associated with a significant decrease in weight gain/food intake, and significant suppression of horizontal locomotion and rearing behaviours; however, grooming activity increased significantly. Also, there was a significant reduction of open-arm time in the EPM and a significant increase in Y-maze alternation (at the lowest concentration of ADA). ADA-containing diet was not associated with significant changes in brain oxidative status or neuromorphology. Conclusion: The study showed that while ADA-containing diet may alter neurobehaviour in rats; this was not associated with evidence of brain oxidative stress or neuro-histomorphological alterations.

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Alterations in behaviour, cerebral cortical morphology and cerebral oxidative stress markers following aspartame ingestion

Cited by 46 publications

References 97 publications

Effect of developmental NMDAR antagonism with CGP 39551 on aspartame-induced hypothalamic and adrenal gene expression

Effect of developmental NMDAR antagonism with CGP 39551 on aspartame-induced hypothalamic and adrenal gene expression

Evaluation of long‐term effects of artificial sweeteners on rat brain: a biochemical, behavioral, and histological study

An Assessment of the Effects of Azodicarbonamide-containing Diet on Neurobehaviour, Brain Antioxidant Status and Membrane Lipid Peroxidation Status in Rats

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