Magnesium L-Threonate Reduces Hippocampal Amyloid-β Load without Cognitive Improvement in a PTU-induced Hypothyroidism Model in Young Rats.

The brain is among the most critical target organs for thyroid hormones. Therefore, both congenital and acquired hypothyroidism can have significant neuropsychiatric consequences. Learning and memory problems, concentration disorders, and some psychiatric disorders such as depression can be observed in diseases causing acquired hypothyroidism. Although thyroid hormone therapy is the standard treatment, it does not always fully reverse these neuropsychiatric complications. Several studies have demonstrated the positive effects of magnesium L-threonate (MgT) supplementation on cognitive functions. Research suggests that MgT may help alleviate cognitive deficits, particularly in neurodegenerative conditions like Alzheimer's disease, where it has been associated with improvements in memory and reductions in hippocampal amyloid-β accumulation. However, there is limited data on the effect of MgT supplementation on hypothyroid conditions in the brain. The purpose of this study was to evaluate the effects of MgT supplementation on cognitive functions in hypothyroid rats. We report that while MgT supplementation did not significantly improve cognitive performance in behavioral tasks or inflammatory markers in hypothyroid rats, it did increase hippocampal BDNF levels in euthyroid animals and reduced hippocampal amyloid-β load under both euthyroid and hypothyroid conditions. The reduction in amyloid beta load under hypothyroid conditions suggests that MgT may exert partial therapeutic effects even in the absence of thyroid hormone replacement. These findings highlight the need for further studies to evaluate the therapeutic potential of MgT, particularly in combination with thyroid hormone replacement.