title: Protocatechuic acid ameliorates neurocognitive functions impairment induced by chronic intermittent hypoxia.
abstract: Chronic intermittent hypoxia (CIH) is a serious consequence of obstructive sleep apnoea (OSA) and has deleterious effects on central neurons and neurocognitive functions. This study examined if protocatechuic acid (PCA) could improve learning and memory functions of rats exposed to CIH conditions and explore potential mechanisms. Neurocognitive functions were evaluated in male SD rats by step-through passive avoidance test and Morris water maze assay following exposure to CIH or room air conditions. Ultrastructure changes were investigated with transmission electron microscopy, and neuron apoptosis was confirmed by TUNEL assays. Ultrastructure changes were investigated with transmission electron microscope and neuron apoptosis was confirmed by TUNEL assays. The effects of PCA on oxidative stress, apoptosis, and brain IL-1β levels were investigated. Expression of Bcl-2, Bax, Cleaved Caspase-3, c-fos, SYN, BDNF and pro-BDNF were also studied along with JNK, P38 and ERK phosphorylation to elucidate the molecular mechanisms of PCA action. PCA was seen to enhance learning and memory ability, and alleviate oxidative stress, apoptosis and glial proliferation following CIH exposure in rats. In addition, PCA administration also decreased the level of IL-1β in brain and increased the expression of BDNF and SYN. We conclude that PCA administration will ameliorate CIH-induced cognitive dysfunctions.
authors.affiliation: School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, Shandong, 264003, China.|Department of respiration, Binzhou Medical University Hospital, Binzhou, Shandong, 256603, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Yin
authors.affiliation: School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, Shandong, 264003, China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of respiration, Binzhou Medical University Hospital, Binzhou, Shandong, 256603, China.
authors.forename: Changjun
authors.initials: C
authors.lastname: Lv
authors.affiliation: School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, Shandong, 264003, China.|Department of respiration, Binzhou Medical University Hospital, Binzhou, Shandong, 256603, China.
authors.forename: Chunli
authors.initials: C
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, Shandong, 264003, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of respiration, Binzhou Medical University Hospital, Binzhou, Shandong, 256603, China.
authors.forename: Xiaozhi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of respiration, Binzhou Medical University Hospital, Binzhou, Shandong, 256603, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Han
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D062385:Hydroxybenzoates / Q000494:pharmacology*; D000860:Hypoxia / Q000150:complications* / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007858:Learning / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D009473:Neuronal Plasticity; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D018384:Oxidative Stress; D010766:Phosphorylation; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020181:Sleep Apnea, Obstructive / Q000150:complications / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D004365:Drugs, Chinese Herbal; D062385:Hydroxybenzoates; D053583:Interleukin-1beta; D011498:Protein Precursors; C426674:brain-derived neurotrophic factor precursor; C009091:protocatechuic acid; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases