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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-1? 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-1? in brain and increased the expression of BDNF and SYN. We conclude that PCA administration will ameliorate CIH-induced cognitive dysfunctions.

SUBMITTER: Yin X

PROVIDER: S-EPMC4588513 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Protocatechuic acid ameliorates neurocognitive functions impairment induced by chronic intermittent hypoxia.

Yin Xue X Zhang Xiuli X Lv Changjun C Li Chunli C Yu Yan Y Wang Xiaozhi X Han Fang F

Scientific reports 20150930

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 conditi ...[more]

PMID: 26419512

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Project description:NEW FINDINGS:What is the central question of this study? Periodic decreases in arterial blood O2 or chronic intermittent hypoxia (CIH) is a hallmark feature of sleep apnoea patients. Despite a large body of clinical evidence linking sleep disordered breathing with apnoeas to diabetes, the causal relationships between CIH and ?-cell function and the underlying molecular mechanisms have not been established. What is the main finding and its importance? In a rodent model, we show that mitochondrial oxidative stress generated by CIH leads to pancreatic ?-cell dysfunction manifested by augmented basal insulin secretion, insulin resistance, defective proinsulin processing and impaired glucose-stimulated insulin secretion. The results of the present study provide evidence for direct effects of CIH on ?-cell function, which may be an underlying molecular mechanism contributing to the development of type 2 diabetes among sleep apnoea patients. Breathing disorders with recurrent apnoea produce periodic decreases in arterial blood O2, i.e. chronic intermittent hypoxia (CIH). Recurrent apnoea patients and CIH-exposed rodents exhibit several co-morbidities, including diabetes. However, the effects of CIH on pancreatic ?-cell function are not known. In the present study, we investigated pancreatic ?-cell function in C57BL6 mice exposed to 30 days of CIH. Compared with control animals, the CIH-exposed mice exhibited elevated levels of fasting plasma insulin but comparable glucose levels and higher homeostasis model assessment, indicating insulin resistance. Pancreatic ?-cell morphology was unaltered in CIH-exposed mice. Insulin content was decreased in CIH-exposed ?-cells, and this effect was associated with increased proinsulin levels. The mRNA and protein levels of the enzyme prohormone convertase 1, which converts proinsulin to insulin, were downregulated in CIH-treated islets. More importantly, glucose-stimulated insulin secretion was impaired in CIH-exposed mice and in isolated islets. Mitochondrial levels of reactive oxygen species (ROS) were elevated in CIH-exposed pancreatic islets. Treatment of mice with mito-tempol, a scavenger of mitochondrial ROS, during exposure to CIH prevented the augmented insulin secretion and restored the proinsulin and homeostasis model assessment values to control levels. These results demonstrate that CIH leads to pancreatic ?-cell dysfunction, manifested by augmented basal insulin secretion, insulin resistance, defective proinsulin processing, impaired glucose-stimulated insulin secretion and increased mitochondrial ROS, which mediate the effects of CIH on pancreatic ?-cell function.

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Protocatechuic acid ameliorates neurocognitive functions impairment induced by chronic intermittent hypoxia.

Publications

Protocatechuic acid ameliorates neurocognitive functions impairment induced by chronic intermittent hypoxia.

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