Expression of Bcl-2 and Bax proteins in hippocampus of rats with abnormal thyroid function and its relationship with cognitive Impairment

Abstract

Objective To investigate the relationship between apoptotic protein Bcl-2 and Bax in rat hippocampal neurons and cognitive dysfunction in rats with abnormal thyroid function. Methods Thirty healthy Wistar rats of 8-week-old SPF grade were randomly divided into three groups: (1) Normal control group (n=10) ; (2) hypothyroidism group (n=10) ; (3) hyperthyroidism group (n=10) .All rats were sacrificed at the 4th week by heart blood sampling. The serum T3 and T4, TSH were measured. Morris water maze was used to train rats in each group for 6 days. At the end of the experiment, the hippocampus was taken from the rats, and HE staining was performed. The expression of apoptotic protein bcl-2 and Bax in rat hippocampal neurons was detected by immunohistochemistry. Results ① The escape latency of hyperthyroidism and hypothyroidism group was higher than that of the normal group at different time points (P 0.05) . ② Hippocampus tissue HE staining: normal control group hippocampal neurons neatly arranged, the shape of the structure was complete and uniform, the nucleus was round or oval, nucleolus obvious, chromatin uniform level and more clear, nucleus round or oval, obviously, hyperthyroidism group, hypothyroidism group of neuronal structure loose, the number decreased, arranged disorder, deep nuclear staining, shrinkage, nucleolus disappeared, cytoplasm around the empty halo, cell spacing larger. ③The positive cells expressing Bcl-2 and Bax protein in the hyperthyroidism group and the hypothyroidism group were increased compared with the normal control group (P<0.05) . Compareds with hyperthyroidism group, the expression of Bcl-2 positive cells was increased in hypothyroidism (P<0.05) . Conclusions ① The spatial learning and memory abilities of the rats with hypothyroidism and the hyperthyroid are lower than those in the normal control group.②The number of apoptotic protein positive cells in Bcl-2 and Bax neurons of hippocampus in rats with hypothyroidism and hyperthyroid increased, and the proportion of Bcl-2 and Bax was impaired,which indicates that apoptosis occurred in hippocampal neurons. This process may be one of the pathogenesis of cognitive impairment. Key words: Thyroid dysfunction; Cognitive function; Hippocampus; Bcl-2; Bax