Dexmedetomidine mediates the mechanism of action of ferroptosis in mice with Alzheimer's disease by regulating the mTOR-TFR1 pathway.

BACKGROUND

Alzheimer's disease (AD) is the most common neurodegenerative disorder, and there are currently no effective drugs to delay progression of the disease. Ferroptosis may play a vital part in AD, and is therefore receiving increasing attention by researchers.

AIM

To investigate the effects of dexmedetomidine (Dex) on ferroptosis in AD mouse hippocampus.

METHODS

Hippocampal neurons (HNs) HT22 were induced by amyloid β-protein (Aβ) and both and AD mouse models were prepared injections. The cell-counting kit-8 assay and immunofluorescence technique were adopted to determine cell proliferation activity and intracellular Fe levels, and the TBA method and microplate method were employed for malondialdehyde and glutathione measurements, respectively. Hippocampal tissue damage was determined using hematoxylin and eosin and Nissl staining. Mouse learning and memory ability in each group was assessed by the Morris water maze test, and the expression levels of mammalian target of rapamycin (mTOR) signal molecules and ferroptosis-related proteins transferrin receptor 1 (TFR1), SLC7A11 and glutathione peroxidase 4 were examined by western blotting.

RESULTS

Dex enhanced lipid peroxidation and iron influx in mouse HNs in both and experiments, while inhibition of the mTOR axis blocked this process. These findings demonstrate that Dex can inhibit ferroptosis-induced damage in mouse HNs by activating mTOR-TFR1 signaling to regulate ferroptosis-associated proteins, thus alleviating cognitive dysfunction in AD mice.

CONCLUSION

Dex can activate the mTOR-TFR1 axis to inhibit ferroptosis in mouse HNs, thereby improving the learning and memory ability of mice.