Protocatechuic Acid Ameliorates Neurocognitive Functions Impairment Induced By Chronic Intermittent Hypoxia

OBJECTIVE:Chronic intermittent hypoxia (CIH) is an underlying component of obstructive sleep apnoea (OSA) and has been shown to have deleterious and damaging effects on central neurons and to impair neurocognitive functions. Neurocognitive impairment induced by CIH has been attributed to several factors including increased oxidative stress, apoptosis, inflammation, altered synaptic plasticity and decreased BDNF. This multifactorial response of the brain to CIH limits the use of therapeutic agents that target individual pathways for ameliorating learning and memory impairment induced by CIH. The present study aimed at exploring the therapeutic potential of protocatechuic acid (PCA) in improving the learning and memory functions of rats in CIH conditions and potential mechanisms.METHODS:The neurocognitive functions were evaluated in male Sprague Dawley rats by step-through passive avoidance test and Morris water maze assay following exposure to CIH conditions.Ultrastructure changes were investigated with transmission electron microscope and neurons apoptosis was confirmed by terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assays. The effects of PCA administration on oxidative stress, apoptosis, and brain Il-1? levels were also investigated. Expression of Bcl-2, Bax, Cleaved Caspase-3, c-fos, SYN, m-BDNF and pro-BDNF were also studied along with JNK and P38 phosphorylation to elucidate the molecular mechanisms of PCA action.RESULTS:PCA administration was seen to enhance learning and memory ability in rats, and alleviate oxidative stress, apoptosis and glial proliferation following CIH exposure. In addition, PCA administration also decreased the level of IL-1? in brain and increased the expression of BDNF and SYN in rats brain.CONCLUSION:Hence, administration of PCA could be a useful therapeutic strategy in ameliorating CIH induced cognitive dysfunctions.