Effect of perinatal hypothyroidism on hippocampal neuronal structure and function of neonatal rats

Abstract

Objective To study the effect of perinatal hypothyroidism (PHT) on hippocampal neuronal structure and function of neonatal rats. Methods Sixteen pregnant SD rats were randomly divided into control group and PHT group (n=8). The pregnant rats were subjected to gavage by normal saline or 6- propyl-2-thiouracil (PTU) every day from 15 d of pregnant to the end of lactation. After parturition, 38 male neonatal rats from each group were chosen for the following study. On the 7th d of birth, 15 neonatal rats from each group were sacrificed, and the concentrations of free triiodothyronine (FT) 3, FT4 and thyroid stimulating hormone (TSH) in serum and acetylcholine (Ach) in the hippocampus were detected by ELISA. Real- time PCR, Western blotting and immunohistochemistry were used to assess the expressions of neuronal nuclei antigen (NeuN) and microtubule- associated protein tau (MAPT) in transcriptional and protein levels orderly. The left neonatal rats at one month old were performed morris water maze test to evaluate the learning and memory abilities. Results ELISA results showed that both FT3 and FT4 significantly decreased but TSH increased significantly in serum of PHT rats as compared with those in the control group (P<0.05); Ach in the hippocampus of PHT rats was reduced three folds as compared with those in control group, with significant difference (P<0.05). Real-time PCR and Western blotting results showed that the mRNA and protein expressionlevels of NeuN and MAPT in PHT rats were markedly down-regulated as compared with those in the control group: 0.25 and 0.12 fold of mRNA level in control group, and 0.35 and 0.22 fold of protein level in control group, with significant differences (P<0.05). Immunohistochemistry indicated decreased NeuN and MAPT expression levels of varying degrees in PHT rats. In the morris water maze, one-month-old rats with PHT showed significantly prolonged escape latency ([10.18±3.02] s) and lengthened total distance ([365.28±41.77] cm) as compared with the control rats ([24.36±5.15] s, [790.36±72.53] cm, P<0.05). Conclusion PHT could result in reduced expressions of neuron markers, axons dysfunction and decreased secretion of neurotransmitter in the hippocampus of neonatal rats, and it could weaken the learning and memory abilities in long term. Key words: Perinatal hypothyroidism; Neuron; Learning and memory ability; Hippocampus