Sex-Specific Anxiety and Prefrontal Cortex Glutamatergic Dysregulation Are Long-Term Consequences of Pre-and Postnatal Exposure to Hypercaloric Diet in a Rat Model

Both maternal and early life malnutrition can cause long-term behavioral changes in the offspring, which depends on the caloric availability and the timing of the exposure. Here we investigated in a rat model whether a high-caloric palatable diet given to the mother and/or to the offspring during the perinatal and/or postnatal period might dysregulate emotional behavior and prefrontal cortex function in the offspring at adult age. To this end, we examined both anxiety responses and the mRNA/protein expression of glutamatergic, GABAergic and endocannabinoid signaling pathways in the prefrontal cortex of adult offspring. Male animals born from mothers fed the palatable diet, and who continued with this diet after weaning, exhibited anxiety associated with an overexpression of the mRNA of Grin1, Gria1 and Grm5 glutamate receptors in the prefrontal cortex. In addition, these animals had a reduced expression of the endocannabinoid system, the main inhibitory retrograde input to glutamate synapses, reflected in a decrease of the Cnr1 receptor and the Nape-pld enzyme. In conclusion, a hypercaloric maternal diet induces sex-dependent anxiety, associated with alterations in both glutamatergic and cannabinoid signaling in the prefrontal cortex, which are accentuated with the continuation of the palatable diet during the life of the offspring.

Withdrawal from Extended, Intermittent Access to A Highly Palatable Diet Impairs Hippocampal Memory Function and Neurogenesis: Effects of Memantine

Background: Compulsive eating can be promoted by intermittent access to palatable food and is often accompanied by cognitive deficits and reduction in hippocampal plasticity. Here, we investigated the effects of intermittent access to palatable food on hippocampal function and neurogenesis. Methods: Male Wistar rats were either fed chow for 7 days/week (Chow/Chow group), or fed chow intermittently for 5 days/week followed by a palatable diet for 2 days/week (Chow/Palatable group). Hippocampal function and neurogenesis were assessed either during withdrawal or following renewed access to palatable food. Furthermore, the ability of the uncompetitive N-methyl-d-aspartate receptor (NMDAR) antagonist memantine to prevent the diet-induced memory deficits and block the maladaptive feeding was tested. Results: Palatable food withdrawn Chow/Palatable rats showed both a weakened ability for contextual spatial processing and a bias in their preference for a “novel cue” over a “novel place,” compared to controls. They also showed reduced expression of immature neurons in the dentate gyrus of the hippocampus as well as a withdrawal-dependent decrease of proliferating cells. Memantine treatment was able both to reverse the memory deficits and to reduce the excessive intake of palatable diet and the withdrawal-induced hypophagia in food cycling rats. Conclusions: In summary, our results provide evidence that withdrawal from highly palatable food produces NMDAR-dependent deficits in hippocampal function and a reduction in hippocampal neurogenesis.

Antiobesity Activity of Flavanoids Isolated from Solanum macrocarpum in Wistar Rats

Aims: To correlate obesity/atherosclerosis with body mass index, serum cholesterol, serum triglyceride, serum low density lipoprotein and serum high density lipoprotein of diet induced obese wistar rats. Study Design: Department of Home Science, Nutrition and Dietetics (Animal research house) and Department of veterinary science both in University of Nigeria Nsukka. The study was conducted between January to March 2012. Methodology: Four groups of twenty male Wistar rats were fed a highly palatable diet for 2 weeks to induce obesity resembling mild obesity condition in human population after one week acclimatization period. DIO rats received rat chow and flavonoids extract daily for 6 weeks. Group 1 received rat chow alone; Group 2- 0.05% of flavonoids extract and rat chow; Group 3- 0.15% of flavonoid extract and rat chow; and Group 4- 0.25% of flavonoid extract and rat chow. BMI, Total cholesterol, HDL, LDL and Triglyceride were evaluated using standard assay technique. The data were statistically analyzed using ANOVA and mean separated using LSD. Results: Feeding the rats with palatable diet showed increased in BMI (from 0.35-0.40 to 0.60-0.65), total cholesterol, LDL and triglyceride levels along with decrease in HDL (p<0.05). Consumption of flavonoids resulted in the significant reduction in BMI, LDL, total cholesterol and triglyceride level and exhibit significant elevation in HDL cholesterol compared to the rats fed only rat chow (p<0.05). It was observed that the decrease in BMI, Triglyceride, total cholesterol and LDL cholesterol level of rats fed 0.25% of flavonoids were significantly different (p<0.05) from those fed 0.15% and 0.05% flavonoids. Conclusions: The results suggest that flavonoids extract from Solanum macranthum has atherogenic effect which can help to reduce obesity.