NEUROCHEMICAL JOURNAL, cilt.19, sa.1, ss.81-91, 2025 (SCI-Expanded)
Thyroid hormone dysfunction may affect intracellular signaling cascades and have a role in regulating cognitive function, particularly in brain areas associated with learning and memory. The study aims to show the effect of curcumin supplementation on long-term potentiation (LTP) under conditions of hypothyroidism and to elucidate changes in the pathways thought to play a key role in cognitive dysfunctions associated with hypothyroidism. Hypothyroidism was induced by administering propylthiouracil (PTU; 0.05%) through drinking water and curcumin was intraperitoneally (Ip) administered through daily injection (70 mg/kg/day). The slope of field excitatory-postsynaptic potential (fEPSP) and population spike (PS) were evaluated by applying high-frequency stimulation (HFS) in the hippocampal dentate gyrus (DG). Total and phosphorylated tau, kinases and phosphatases in the whole hippocampus were determined by using western blotting. The study results showed that PTU treatment impaired the LTP of both the dendritic fEPSP slope and somatic PS amplitude in the hippocampal DG in rats. While, curcumin supplementation restored the impaired LTP observed in the PTU treated rats. Additionally, PTU treatment increased the phosphorylation of GSK3 beta at Ser9. However, there was no increase in p-GSK3 beta in the hippocampal DG induced by HFS with curcumin supplementation. Also, there was an increase in total and phosphorylated PP2A when compared to the control rats in the hippocampal DG induced by HFS in both hypothyroid and curcumin supplemented hypothyroid rats. These results suggested that curcumin supplementation may improve hippocampal synaptic plasticity disrupted with hypothyroidism. We concluded that hypothyroidism could trigger an unusual mechanism during LTP by altering p-GSK3 beta and PP2A activities. Thereby detailed studies to reveal more precise evidence for the use of curcumin as a therapeutic target in cognitive disorders are needed.