Thyroxine Disrupts Synaptic Plasticity via Non-genomic Action in the Hippocampus

甲状腺素通过非基因组作用干扰海马体的突触可塑性

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Abstract

OBJECTIVE: Numerous neurological deficiency disorders are caused by the thyroid hormones' early-life modulatory actions, which persist throughout adulthood. Pairing-pulse facilitation is used to assess hippocampal short-term plasticity, while long-term potentiation (LTP) is used to assess long-term plasticity. Thyroid hormones target the genes that cause synaptic plasticity to occur. This study focused on the non-genomic effects of T4 hormone in the hippocampus. METHODS: After a 15-minute baseline recording, LTP was induced by applying high-frequency stimulation protocols. Infusions of artificial cerebrospinal fluid (aCSF) or L-thyroxine were performed during the stimulation protocols. We performed real-time quantitative polymerase chain reaction (RT-qPCR) to determine whether there was a difference in gene expression levels in the hippocampi of rats infuse with aCSF or T4 and how this correlated with LTP responses. RESULTS: T4 infusion was observed to impair LTP. T4 increased CREB and GluN2B expression in all groups while decreasing GluN1 expression in unstimulated hippocampi and increasing it during the induction phase of LTP. It decreased GluN2A expression during the induction phase of LTP. During the maintenance phase of LTP, T4 prevented the increase in Elk-1 and p38MAPK expression levels observed in the aCSF group. CONCLUSION: When we evaluated LTP responses together with RT-qPCR analyses, we found that T4 impaired LTP responses and increased CREB and GluN2B expression. T4's reduction of GluN2A expression levels may be responsible for the impairment during the induction phase of LTP, while its inhibition of the increase in Elk-1 expression may be responsible for the impairment observed during the maintenance phase of LTP.

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