Nitric oxide contributes to learning and memory deficits observed in hypothyroid rats during neonatal and juvenile growth

INTRODUCTION: Severe cognitive impairment follows thyroid hormone deficiency during the neonatal period. The role of nitric oxide (NO) in learning and memory has been widely investigated. METHODS: This study aimed to investigate the effect of hypothyroidism during neonatal and juvenile periods on NO metabolites in the hippocampi of rats and on learning and memory. Animals were divided into two groups and treated for 60 days from the first day of lactation. The control group received regular water, whereas animals in a separate group were given water supplemented with 0.03% methimazole to induce hypothyroidism. Male offspring were selected and tested in the Morris water maze. Samples of blood were collected to measure the metabolites of NO, NO2, NO3 and thyroxine. The animals were then sacrificed, and their hippocampi were removed to measure the tissue concentrations of NO2 and NO3. DISCUSSION: Compared to the control group's offspring, serum thyroxine levels in the methimazole group's offspring were significantly lower (P<0.01). In addition, the swim distance and time latency were significantly higher in the methimazole group (P<0.001), and the time spent by this group in the target quadrant (Q1) during the probe trial was significantly lower (P<0.001). There was no significant difference in the plasma levels of NO metabolites between the two groups; however, significantly higher NO metabolite levels in the hippocampi of the methimazole group were observed compared to controls (P<0.05). CONCLUSION: These results suggest that the increased NO level in the hippocampus may play a role in the learning and memory deficits observed in childhood hypothyroidism; however, the precise underlying mechanism(s) remains to be elucidated

Brain Tissues Oxidative Damage as a Possible Mechanism of Deleterious Effects of Propylthiouracil- Induced Hypothyroidism on Learning and Memory in Neonatal and Juvenile Growth in Rats

Introduction: The role of brain tissues oxidative damage in learning and memory impairments has been well documented. It is also well known that thyroid hormones have a critical role for the brain functions. The purpose of this study was to investigate the role of brain tissues oxidative damage as a possible mechanism of deleterious effects of propylthiouracil (PTU) - induced hypothyroidism on learning and memory in neonatal and juvenile growth in rats. Methods: Fourteen pregnant female Wistar rats were kept in separate cages. After delivery, they were randomly divided into two groups including control and PTU. Rats in the control group received normal drinking water, whereas the second group received drinking water supplemented with 0.02% PTU from the first day after delivery through the first two months of the life of offspring (the pups of rats). After 60 days, nine male offspring of each group were randomly selected and tested in the Morris water maze (MWM). Then, samples of blood were collected to measure thyroxine. Finally, the brains were removed and total thiol groups and molondialdehyde (MDA) concentrations were determined. Results: Compared to the control group’s offspring, serum thyroxine levels in the PTU group’s off spring were significantly low (P<0.001). In MWM, the escape latency and traveled path in the PTU group were significantly higher than that in the control group (P<0.01- P<0.001). In PTU group, the total thiol concentrations in both cortical and hippocampal tissues were significantly lower and MDA concentrations were higher than control group (P<0.001). Discussion: It seems that deleterious effect of hypothyroidism during neonatal and juvenile growth on learning and memory is at least in part due to brain tissues oxidative damage