Sleep Deprivation Induces Ferroptosis and Reduces the Expression of GABAB Receptor in Mice

Ferroptosis, a form of regulated cell death characterized by iron-dependent lipid peroxidation, has emerged as a critical mechanism underlying the pathophysiological effects of sleep deprivation (SD) and neurological consequences. Recent studies have highlighted the significant neuroprotective role of the GABA_B receptor. This study aimed to investigate the effects of SD-induced ferroptosis on the expression of the GABA_B receptor in the hippocampus. Thirty-six male C57BL/6 mice were used in this study, with twenty-four subjected to SD through a modified multiple-platform water method and twelve serving as controls. Learning and memory capacities were evaluated using the Morris water maze, while hippocampal neuron morphology was examined via Nissl staining. Biochemical assays were conducted to measure levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and lactate dehydrogenase (LDH) in serum, hippocampal tissue, and cultured cells. Transmission electron microscopy and flow cytometry were employed to observe mitochondrial alterations and reactive oxygen species levels. Western blotting was performed to analyze the expression of the GABA_B receptor and ferroptosis-related proteins. SD resulted in impaired learning and memory, hippocampal neuronal damage, morphological alterations in hippocampal neuronal mitochondria, and abnormal expression of the GABA_B receptor and ferroptosis-related proteins in the hippocampus of mice. Similarly, in vitro experiment, we observed a increase in oxidative stress, mitochondrial structural damage, aberrant expression of the GABA_B receptor, and changes in ferroptosis-related protein levels. SD induced ferroptosis in hippocampal neurons of mice, reduced the expression of the GABA_B receptor, and led to impairments in learning and memory.