Methionine Administration in Pregnant Rats Causes Memory Deficit in the Offspring and Alters Ultrastructure in Brain Tissue

In the present work, we evaluated the effect of gestational hypermethioninemia on locomotor activity, anxiety, memory, and exploratory behavior of rat offspring through the following behavior tests: open field, object recognition, and inhibitory avoidance. Histological analysis was also done in the brain tissue of pups. Wistar female rats received methionine (2.68 μmol/g body weight) by subcutaneous injections during pregnancy. Control rats received saline. Histological analyses were made in brain tissue from 21 and 30 days of age pups. Another group was left to recover until the 30th day of life to perform behavior tests. Results from open field task showed that pups exposed to methionine during intrauterine development spent more time in the center of the arena. In the object recognition memory task, we observed that methionine administration during pregnancy reduced total exploration time of rat offspring during training session. The test session showed that methionine reduced the recognition index. Regarding to inhibitory avoidance task, the decrease in the step-down latency at 1 and 24 h after training demonstrated that maternal hypermethioninemia impaired short-term and long-term memories of rat offspring. Electron microscopy revealed alterations in the ultrastructure of neurons at 21 and 30 days of age. Our findings suggest that the cell morphological changes caused by maternal hypermethioninemia may be, at least partially, associated to the memory deficit of rat offspring.