Inhibition of ERK1/2 regulates cognitive function by decreasing expression levels of PSD-95 in the hippocampus of CIH rats.

Obstructive sleep apnoea syndrome (OSAS) is a potentially severe sleep disorder characterized by intermittent hypoxia, and there is growing evidence that OSAS can lead to cognitive decline. Extracellular signal-regulated protein kinase 1/2 (ERK1/2) plays a key role in synaptic plasticity. We established CIH model in male SD rats and examined their expression of p-ERK1/2 and PSD-95, as well as in CIH group; the effect of SL327 on the expression of p-ERK1/2 and PSD-95 in hippocampus of CIH model rats was observed by pretreating the experimental rats with SL327 during peak time of p-ERK1/2 expression. Mean oxygen saturation in the tail artery was lower in the CIH group. CIH groups exhibited increased escape latencies in the navigation test and decreased numbers of platform crossings in the space exploration test. Reduced volume, irregular structure, deepened cytoplasmic eosinophilic staining in the cytoplasm and decreased nuclear size were found in hippocampal neurons in the 28-d CIH and 28-d CIH + SL327 group. The hippocampus of CIH rats' p-ERK expressions gradually increased with prolonged CIH exposure but decreased after SL327 treatment. Moreover, PSD-95 expressions gradually reduced in the 14-d CIH, 21-d CIH and 28-d CIH groups but increased in the SL327-treated group. The SL327 intervention decreased p-ERK1/2 expression, increased PSD-95 expression and improved cognitive function in CIH rats. The present findings provide some insights into the mechanisms underlying OSAS-associated cognitive impairment.