Fabiana Cardoso Vilela

Gestational hypothyroidism is a prevalent disorder in pregnant women and also impairs fetal development with relevant outcomes. One of the outcomes of greatest interest has been rodent fear‐ and anxiety‐like behavior. However, the relationship between maternal hypothyroidism and onset of conditioned fear‐related responses in offspring remains controversial. Here, we used a well‐validated methimazole‐induced gestational hypothyroidism to investigate the behavioral consequences in offspring. Dams were treated with methimazole at 0.02% in drinking water up to gestational Day 9. Maternal body weights and maternal behavior were evaluated, and the puppies ware analyzed for weight gain and physical/behavioral development and assigned for the open field and fear conditioning test. Methimazole‐induced gestational hypothyroidism induced loss in maternal and litter weight, increases in maternal behavior, and impairs in offspring developmental landmarks in both male and female rodents. Only male offspring enhanced responsiveness to conditioned fear‐like behavior in adulthood.

The consumption of a hypercaloric diet leads to an increase in obesity, which can lead to an inflammatory state. Thus, the objective of this work was to analyze the influence of this inflammation on the behavior of obese animals. For this, male Swiss mice were kept under controlled feeding were divided into 2 groups; Group Cafeteria diet, which received high calorie foods and standard chow for rodent, while the control group received only standard rat chow. After 30 days, 2 hours before the behavioral tests, both groups were subdivided, so that half of the animals of each group received LPS by intraperitoneal injection (100 g/kg; i.p.) and the other half received saline injection ( 0.9% NaCl, 100g/kg; i.p.) (Groups: Cafeteria Diet + LPS and Cafeteria Diet + Saline; Normal Diet + LPS and Normal Diet + Saline). Afterwards, they were submitted to the Open Field Test and the Forced Swim Test and later euthanized for collection and weighing of the epididymal and retroperitoneal adipose tissue. There was an increase in weight, epididymal and retroperitoneal fat in mice treated with cafeteria diet compared to normal diet. LPS had a more pronounced effect in the cafeteria diet group, with a decrease in the number of entries in the periphery and in the center, in addition to the total number of entries and rearing, in the open field test. There was also an increase in time floating in the forced swim test. Therefore, the accumulation of body fat, by the ingestion of a hypercaloric diet, potentiates the inflammatory state caused by LPS, leading to an anxiogenic effect.

Glyphosate is the organophosphate pesticide most widely used in the world. Recent studies correlate exposure to glyphosate and the emergence of neurodevelopmental disorders. Therefore, it was objective to propose a rat model of perinatal exposure to glyphosate‐based herbicides (GBH) to study associated neurodevelopmental disorders. Behavioral aspects and brain pathways were assessed in the prepubertal phase. For this, maternal treatment occurred throughout the entire gestation period (from GD0) until weaning on postnatal day 22 (PND 22). Control group received oral gavage with 5 mL/kg of saline per day and GBH group received oral gavage with 50 mg/kg of GBH per day (n = 10 per group). Maternal behavior was evaluated in PND 2–6. Offspring were evaluated for quantification of ultrasonic vocalizations (PND 5); homing behavior test (PND 13); and hole board, social play behavior, open field, and object recognition tests (PND 28–32). Prefrontal cortex and hippocampus of the offspring were processed to evaluate oxidative stress. Maternal exposure to GBH impaired early social communication, olfactory discrimination, social play behavior, and the exploration of objects, in addition to increasing repetitive and stereotyped movements. GBH also increased oxidative stress. Therefore, perinatal GBH exposure induced behavioral and oxidative stress impairments in rats associated with neurodevelopmental disorders. The manifestations found in the offspring are in accordance with symptoms of autism spectrum disorder.