Prenatal LPS exposure increases hippocampus IL-10 and prevents short-term memory loss in the male adolescent offspring of high-fat diet fed dams.

Lipopolysaccharide (LPS) tolerance can reduce the neuroinflammation caused by high fat maternal diets; however, there are no reports that have evaluated the effects of prenatal LPS exposure on the memories of the offspring of high-fat diet fed dams. This study evaluated the effects of prenatal LPS exposure on the inflammatory parameters and redox status in the brain, as well as the object recognition memory of adolescent offspring of Wistar rat dams that were treated with a high-fat diet during gestation and lactation. Female pregnant Wistar rats randomly received a standard diet (17.5% fat) or a high-fat diet (45.0% fat) during gestation and lactation. On gestation days 8, 10, and 12, half of the females in each group were intraperitoneally treated with LPS (0.1 mg.kg-1). After weaning, the male offspring were placed in cages in standard conditions, and at 6 weeks old, animals underwent the novel object recognition test (for short- and long-term memory). The offspring of the high-fat diet fed dams showed increased hippocampus IL-6 levels (21-days-old) and impaired short-term memories. These effects were avoided in the offspring of high-fat diet fed dams submitted to prenatal LPS exposure, which showed greater hippocampus IL-10 levels (at 21- and 50-days-old), increased antioxidant activity (50-days-old) in the hippocampus and prefrontal cortex, without memory impairments (short- and long-term memory). IL-6 has been consistently implicated in memory deficits and as an endogenous mechanism for limiting plasticity, while IL-10 regulates glial activation and has a strong association with improvements in cognitive function. Prenatal LPS exposure preventing the increase of IL-6 in the hippocampus and the impairment to short-term object recognition memory caused by the high-fat maternal diet.

LPS tolerance prevents anxiety-like behavior and amygdala inflammation of high-fat-fed dams' adolescent offspring.

Maternal high-fat diets (HFD) can generate inflammation in the offspring's amygdala, which can lead to anxiety-like behaviors. Conversely, lipopolysaccharide (LPS) tolerance can reduce neuroinflammation in the offspring caused by maternal high-fat diets. This study evaluated the combination of LPS tolerance and high-fat maternal diet on amygdala's inflammatory parameters and the anxiety-like behavior in adolescent offspring. Female pregnant Wistar rats received randomly a standard diet or a high-fat diet during gestation and lactation. On gestation days 8, 10, and 12, half of the females in each group were intraperitonially injected with LPS (0.1 mg.kg-1). After weaning, the male offspring (n = 96) were placed in individual boxes in standard conditions, and when 6 weeks-old, the animals underwent: Open-Field, Light/Dark Box, Elevated Plus-Maze, and Rotarod tests. When 50 days-old the offspring were euthanized and the amygdala removed for cytokine and redox status analysis. The offspring in the HFD group showed lower amygdala IL-10 levels, high IL-6/IL-10 ratio, and anxiety-like behaviors. These effects were attenuated in the HFD offspring submitted to LPS tolerance, which showed an anti-inflammatory compensatory response in the amygdala. Also, this group showed a higher activity of the enzyme catalase in the amygdala. In addition, receiving the combination of LPS tolerance and maternal HFD did not lead to anxiety-like behavior in the offspring. The results suggest that LPS tolerance attenuated amygdala inflammation through an anti-inflammatory compensatory response besides preventing anxiety-like behavior caused by the high-fat maternal diet.

Caloric restriction or cafeteria diet from birth to adulthood increases the sensitivity to ephedrine in anxiety and locomotion in Wistar rats.

INTRODUCTION: Obesity and undernutrition, consequences of malnutrition, have been linked to the development of mental illnesses. Both states have been linked to increased sensitivity to some drugs, but there are few data for this association considering drugs with noradrenergic-dopaminergic action. OBJECTIVE: To evaluate the nutritional status of animals treated with either a caloric restriction (CR) or cafeteria (CAF) diet from birth and their behavior after ephedrine application. METHODS: During the lactation period, 12 litters of Wistar rats (dam + 8 pups) were fed one of three diets: control (n = 4), CR (n = 4), and CAF (n = 4). After weaning, the males were placed in individual boxes and received the same diet as their respective dams. Nutritional assessments were performed after weaning and in adulthood. In adulthood, males received either saline or ephedrine (20 mg/kg) and underwent behavioral tests including the elevated plus-maze, open-field, and food intake tests. RESULTS: The CR group exhibited higher serum high-density lipoprotein (HDL) levels and lower food and caloric intake, weight gain, and fat mass than the control group. The CAF group exhibited lower food intake and higher fat caloric intake, fat mass, and serum low-density lipoprotein (LDL), triglyceride, total cholesterol, and hepatic lipid levels than the control group. These results indicated that the CR and CAF groups had developed undernutrition and obesity, respectively. In the elevated plus-maze and open-field tests, the CR and CAF groups showed lower anxiety-like behaviors than the control group after ephedrine application. This result indicates that the animal's nutritional status (undernutrition or obesity) can enhance ephedrine sensitivity. CONCLUSION: The CR group exhibited undernutrition, whereas the CAF group exhibited obesity. Ephedrine altered anxiety and locomotion in animals that received the CR and CAF diets in manner different than that observed in animals receiving the standard diet.

Cafeteria diet administered from lactation to adulthood promotes a change in risperidone sensitivity on anxiety, locomotion, memory, and social interaction of Wistar rats.

PURPOSE: To evaluate the nutritional status and behavior of animals fed a cafeteria diet from the onset of lactation after the addition of risperidone. METHODS: During the lactation period, 14 litters of Wistar rats (dam + 8 pups) were fed one of two diets: control (CTRL; n = 7) or cafeteria (CAF; n = 7). After weaning, the males were placed in individual cages, receiving the same diet as offered to their respective dams. Food and caloric intake, body weight, feed and energy efficiency, and adipose tissue weight were evaluated in the male offspring. In adulthood, they were assigned to receive treatment with saline (CTRL-S, CAF-S) or risperidone (CTRL-R, CAF-R) (n = 21 in each group). They then underwent behavioral testing, which included the elevated plus maze, open field, object recognition, and social interaction tests. Variance analysis (ANOVA) was used, followed by Newman-Keuls when p-values were < 0.05. RESULTS: The CAF group exhibited higher caloric intake, weight gain, feed efficiency, and adipose tissue than the CTRL group. The animals in the CAF group exhibited oxidative stress characteristics in the hippocampus, which may have compromised the function of this structure and promoted behavioral changes. The CAF-S group exhibited anxiety, as indicated by the greater number of entrances and time spent in the center of the open field. They also showed greater locomotion through a greater number of quadrants traveled. CAF-S animals also demonstrated memory impairments, assessed using the object recognition test, and decreased social interaction. The CAF-R group demonstrated anxiety and decreased locomotion in the open field. There was a decrease in their interaction with both objects in the object recognition test. The CAF-R group obtained greater sociability in the social interaction test. Such effects may be associated with changes in the serotonergic system of these animals. CONCLUSION: Risperidone administered to animals on a cafeteria diet led to a greater reduction in locomotion, had an anxiogenic effect, caused impaired memory, and improved social interaction.