Maternal L-thyroxine treatment during lactation affects learning and anxiety-like behaviors but not spatial memory in adult rat progeny

Abstract

Background: The present study compared behavioral and molecular indicators of hippocampal function in L-thyroxine treated rats to determine whether thyroid hormone excessiveness produces relatively stable lifelong changes.

Methods: Hyperthyroidism was induced in rats by daily injections of L-thyroxine (0.2 mg/kg) to their dams for lactation period (MOH: maternal-onset hyperthyroidism) or to the rats itself during the young adult period (AOH: adult-onset hyperthyroidism; between the day 39-60). Spatial learning was assessed in the Morris Water Maze (MWM). Levels of type 2 and type 3 deiodinases, Erk1/2, JNK and P38^MAPK were assessed via western blotting in the hippocampus of trained rats. Measurements were all done in rats aged 60-66 days.

Results: In MWM, maternally treated rats with L-thyroxine swam more away from the hidden platform, with showing more anxiety-like behavior, as compared to the rats treated or no treated with L-thyroxine in young adulthood. In spite of impaired acquisition, MOH group was not significantly different from the other groups in probe trial. In Western blot of the hippocampus, a decreased the expression of P38MAPK was found in rats treated with L-thyroxine in young adulthood period. However, maternal treatment with L-thyroxine resulted in an increased expression of Type 2 deiodinase and a tendency toward decreased expression of total and phosphorylated ERK1/2. No detectable band for type 3 deiodinase, p-JNK and p-P38^MAPK was observed in all three groups.

Conclusion: These results suggest that perinatal excessiveness of thyroid hormone has longstanding effects on hippocampal function and may account for memory problems experienced by adolescents with lactational hyperthyroidism.

Keywords: Hippocampus; Lactational hyperthyroidism; Learning and memory; Morris water maze.