Role of Brain-Derived Neurotrophic Factor on Cognition of Hypothyroid Neonatal Rats

Mechanisms underlying the effects of inadequate thyroid hormone availability to the brain, on cognitive functions are not completely understood. The aim of this study is to assess if dysregulation of Brain derived neurotrophic factor (BDNF) through its gene methylation and / or brain oxidative stress state have a role .Fifteen female rats were divided into two groups; control and propylthiouracil hypothyroidism induced group. Offspring of each group were divided into three subgroups for assessment at 3, 7 days and 8 weeks. BDNF protein level, DNA methylation status of BDNF gene, malondialdehyde (MDA) and total antioxidant capacity (TAC) were measured in hippocampal brain tissue. Cognitive functions were assessed through Morris Water Maze (MWM) task to the subgroups of age 8 weeks. Results showed that BDNF protein level was significantly reduced in the hippocampi of maternal hypothyroidism offspring at the developmental stage (3 day and 7 day groups) (p value= <0.001in both groups), which was significantly associated with BDNF gene methylation state. Hippocampal MDA level was significantly increased in pups from hypothyroidism dams at the developmental stage (3 and 7 day groups) (p<0.001 in both groups). MWM task showed that 8 weeks-old maternal hypothyroidism offspring were significantly impaired in their performance (P<0.001) relative to age-matched controls. We conclude that, long-term memory deficits in hypothyroidism maybe caused by the interplay of the DNA methylation of BDNF gene, the excess oxidative stress and deteriorated antioxidant defense system in the brain hippocampus.