Sex-specificities in offspring neurodevelopment and behaviour upon maternal glycation: Putative underlying neurometabolic and synaptic changes.

AIM: Lactation is an important programming window for metabolic disease and neuronal alterations later in life. We aimed to study the effect of maternal glycation during lactation on offspring neurodevelopment and behaviour, assessing possible sex differences and underpinning molecular players. METHODS: Female Wistar rats were treated with Glyoxalase-1 inhibitor S-p-Bromobenzylguthione cyclopentyl diester (BBGC 5 mg/kg). A control and vehicle group treated with dimethyl sulfoxide were also considered. Male and female offspring were tested at infancy for neurodevelopment hallmarks. After weaning, triglycerides and total antioxidant capacity were measured in breast milk. At adolescence, offspring were tested for locomotor ability, anxious-like behaviour, and recognition memory. Metabolic parameters were assessed, and the hippocampus and prefrontal cortex were collected for molecular analysis. KEY FINDINGS: Maternal glycation reduced triglycerides and total antioxidant capacity levels in breast milk. At infancy, both male and female offspring presented an anticipation on the achievement of neurodevelopmental milestones. At adolescence, male offspring exposed to maternal glycation presented hyperlocomotion, whereas offspring of both sexes presented a risk-taking phenotype, accompanied by increase GABAA receptor levels in the hippocampus. Females also demonstrated GABAA and PSD-95 changes in prefrontal cortex. Furthermore, lower levels of GLO1 and consequently higher accumulation of AGES were also observed in both male and female offspring hippocampus. SIGNIFICANCE: Early exposure to maternal glycation induces changes in milk composition leading to neurodevelopment changes at infancy, and sex-specific behavioural and neurometabolic changes at adolescence, further evidencing that lactation period is a critical metabolic programming window and in sculpting behaviour.

Investigation of the antioxidant and hypoglycemiant properties of Alibertia edulis (L.C. Rich.) A.C. Rich. leaves.

ETHNOPHARMACOLOGICAL RELEVANCE: Alibertia edulis (L.C. Rich.) A.C. Rich is a vegetable species used in Brazilian folk medicine due to it is putative hypoglycemiant effect but has never been pharmacologically investigated. It is popularly used for the control of diabetes, especially in the state of Mato Grosso, Brazil. Following confirmation of the antioxidant activity of A. edulis by Aquino et al. (2017), the aim of this study was to evaluate the effects of leaves of A. edulis aqueous extract (AEAE) on some biochemical parameters in mice fed a high-fat fed. MATERIAL AND METHODS: Leaves of A. edulis were air-dried in an oven at 40 °C for 10 days and ground into a fine powder by mechanical milling. The AEAE was prepared by decoction (1:10 w/v) at 97 °C for 15 min, and later filtered and lyophilized. Preliminary phytochemical analysis of the AEAE has been already indetified the presence of caffeic acid, quercetin 3-rhamnosyl-(1 â†’ 6)-galactoside and iridois ioxide, ferulic acid and rutin in decocted leaves (Aquino et al., 2017). In one experiment, the acute oral toxicity AEAE was evaluated at 2,000 mg/kg of body weight. The animals were observed periodically for 14 days. In second experiment, the animals were divided into four groups (n = 5): Control, AEAE 200, AEAE 400 mg/kg and positive control (Metformin 100 mg/kg). In a third experiment, animals were divided into: Control RC (standard diet) (n = 24) and Control HFF (high-fat fed) (n = 24) groups for induction of glucose intolerance. After eight weeks, they were further subdivided into six groups (n = 8 each) RC or HFF with or without AEAE at doses of 200 and 400 mg/kg (2-wk) treatments to assess glucose tolerance. Plasma indicators of glucose tolerance and liver damage, skeletal muscle expression of antioxidant enzymes, and expression of the antioxidant proteins of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and phosphorylated IKK were determined. RESULTS: The HF-fed animals developed glucose intolerance which the AEAE failed to revert. Meanwhile, the AEAE treatment did lower the glucose levels in the normolipidic cohorts by virtue of its antioxidant property. It was also observed that the treatment with the AEAE reduced food intake negatively interfering weight accretion. Beyond that, the treatment with AEAE interfered in the SOD and catalase expression and inhibited phosphorylation of IKK thus suggesting that the observed hypoglycemiant power may be related to its known antioxidant potential. No sings of toxicity or hemolysis were detectaed at indicating that, at the concentrations evaluated, the extract was not toxic to normal cells. CONCLUSION: The AEAE showed a hypoglycemiant effect in the normolipidic mice that received the control diet, but not in those that were made glucose-intolerant by consuming a high-fat fed. The extract also exhibited substantial protection against hemolysis and oxidative stress. Moreover, no signs of toxicity were evident at 2000 mg/kg of body weight.