The disturbance of thyroid-associated hormone and its receptors in brain and blood circulation existed in the early stage of mouse model of Alzheimer’s disease

Abstract

Background: Studies showed that thyroid function plays an important role in the pathology of Alzheimer’s disease (AD). However, changes in brain thyroid hormone and related receptors in the early stage of AD were rarely reported. The aim of this study was to explore the relationship between the early stage of AD and local thyroid hormone and its receptors in the brain. Methods: The animal model was established by stereotactic injection of okadaic acid (OA) into hippocampal region for the experiment, and 0.9% NS for the control. Blood sample from each mouse was collected and then the mice were sacrificed and the brain tissue was collected for detecting free triiodothyronine (FT3), free thyroid hormone (FT4), and thyroid-stimulating hormone (TSH), thyrotropin-releasing hormone (TRH) and phosphorylated tau, amyloid-β (Aβ) and thyroid hormone receptors (THRs) in the hippocampus of the mice were detected as well. Results: Enzyme-linked immunosorbent assay showed that compared with the control, FT3, FT4, TSH and TRH in brain were significantly increased in the experimental group; in the serum, FT4, TSH and TRH were increased, while FT3 had no change; western blot analysis indicated that the expression of THR α and β in the hippocampus of the experimental group was significantly higher than that of the control. Conclusion: Based on the results of this study, a mouse AD model can be established successfully by injecting a small dose of OA into the hippocampus. We speculate that early AD brain and circulating thyroid dysfunction may be an early local and systemic stress repair response.

Thyroid dysfunction and Alzheimer's disease, a vicious circle

“…created an early Alzheimer’s disease (AD) rat model by injecting okadaic acid (OA) into the rats’ hippocampus, which activated GSK-3, increased higher oxidative stress, generated tau hyperphosphorylation, and increased βA neurotoxicity. The study’s findings demonstrated a notable increase in FT3, FT4, TSH, and TRH levels within the brain tissues of rats in the early stages of AD, and there was a notably higher expression of TH receptors in the hippocampal tissues compared to the control group, along with FT4, TSH, and TRH were up in blood, with no change in FT3 ( 28 ). As a result, it came up that the hyperthyroid condition observed in the brain and circulation during early AD could be an early local and systemic stress repair response.…”

Anorexigenic neuropeptides as anti-obesity and neuroprotective agents

“…Moreover TRH could be implicated in the increased excitability of hippocampal CA1 neurons [ 265 ]. On the other hand, in a model of early-stage AD induced by intrahippocampal injection of okadaic acid, which enhances the activity of the Tau kinase GSK-3β and increases Tau phosphorylation, the level of TRH increases in the brain, as does the level of TRH in the blood serum [ 266 ].…”