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

Abstract

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.

The neuroprotective role of melatonin in a gestational hypermethioninemia model

“…If there are morphological changes as adaptation or response to a certain stress, mitochondria can signal survival or cell death depending on the severity of insult (Kasahara and Scorrano, 2014). These data indicate the extent of insult caused by excessive Met in maternal environment and agreed with our recent study (Schweinberger et al, 2017b).…”

“…Since the adequate functioning of Na + , K + ‐ATPase is essential for nerve impulse conduction, the reduction of its activity may also lead to decreased memory and learning capacity (Wyse et al, 2004; Dos Reis‐Lunardelli et al, 2007; Vanzella et al, 2017) and that melatonin partially prevented Na + , K + ‐ATPase activity at 30‐day old pups, in the present study we also evaluated whether melatonin could prevent memory alterations observed in the offspring at 30‐day old born hypermethioninemic rats (Schweinberger et al, 2017b). In the present study we showed that male 30‐day‐old pups exposed to Met during gestation bear learning and memory impairments (water maze tasks).…”

“…The number of pups used in each analysis is reported together with the data shown below the respective figure or table. The experimental design of gestational hypermethioninemia, the days of biochemical, morphological and behavioral analyses were followed as previously published by Schweinberger et al (2014; 2017a; 2017b).…”

“…This technique was performed in cerebral parietal cortex and analyzed as described by Souza (2007) and adapted according to Schweinberger et al (2017b). First, cardiac perfusion was performed with 0.9% saline solution and then with paraformoldehyde 4% plus glutaraldehyde 2.5% in 0.1 M phosphate buffer (PB) at room temperature.…”

“…It was recently shown that gestational hypermethioninemia impaired memory and altered neuron ultrastructure in the offspring at 21 and 30 days of age, suggesting that the cell morphological changes caused by maternal hypermethioninemia may be, at least partly, associated to memory deficits in the rat offspring. Since there is strong evidence that the neurological injury caused by hypermethioninemia occurs due to oxidative stress, antioxidant molecules may be useful to avoid such harmful effects (Schweinberger et al, 2017b).…”