Dimethyl fumarate improves cognitive impairment by enhancing hippocampal brain-derived neurotrophic factor levels in hypothyroid rats.

Background: Dimethyl fumarate (DMF) is an effective drug for multiple sclerosis and can improve the cognitive dysfunction caused by streptozotocin, but the effect on cognitive dysfunction caused by hypothyroidism is unclear.

Methods: After the hypothyroidism rat model induced by propylthiouracil, we gave rats 25 mg/kg DMF by gavage. The body weight during model building and administration was recorded. The levels of T4 and T3 in serum were detected by an automatic biochemical analyzer. Morris water maze test was used to detect the effect of DMF on cognitive learning ability. The effect of DMF on Nissl bodies in the brain tissue was evaluated by Nissl staining. The mRNA and protein levels of BDNF in brain tissue were detected by quantitative reverse transcription-polymerase chain reaction and Western blot. The degrees of p-AKT/AKT and p-CREB/CREB in brain tissue were detected by Western blot.

Results: After DMF treatment, the body weight of hypothyroid rats recovered, and the levels of T3 and T4 in the serum were ameliorated. DMF also reduced the escape latency and distance traveled, and increased the swim speed. The number of Nissl bodies and expression of BDNF, p-AKT/AKT, and p-CREB/CREB in the brain tissue were increased after DMF treatment.

Conclusion: DMF improved the cognitive dysfunction of hypothyroid rats by increasing the level of BDNF in the brain tissue of hypothyroid rats.