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

Yin X, Zhang X, Lv C, Li C, Yu Y, Wang X, Han F - Sci Rep (2015)

Bottom Line: The effects of PCA on oxidative stress, apoptosis, and brain IL-1β levels were investigated.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.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, Shandong, 264003, China.

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.

No MeSH data available.


Related in: MedlinePlus

(A) Western blotting analysis revealed SYN protein bands of hippocampus. (B) SYN positive products (a–c) were brownish yellow granules located in the neuropil. Scale bar = 50 μm. The OD of SYN was shown in a statistical graph (d). The results were expressed as the mean ± SD (n = 3). **P < 0.05 vs. RA group, #P < 0.05 vs. CIH group. (C) Western blotting analysis revealed SYN protein bands of prefrontal cortex. (D) SYN positive products (a–c) were brownish yellow granules located in the neuropil. Scale bar = 50 μm. The OD of SYN was shown in a statistical graph (d). The datas were expressed as the mean ± SD (n = 3). *p < 0.05, **p < 0.01 and ***P < 0.001, vs. the RA group. #p < 0.05, ##p < 0.01 and ###P < 0.001, compared to CIH group. Full-length blots/gels are presented in Supplementary Figure A.
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f5: (A) Western blotting analysis revealed SYN protein bands of hippocampus. (B) SYN positive products (a–c) were brownish yellow granules located in the neuropil. Scale bar = 50 μm. The OD of SYN was shown in a statistical graph (d). The results were expressed as the mean ± SD (n = 3). **P < 0.05 vs. RA group, #P < 0.05 vs. CIH group. (C) Western blotting analysis revealed SYN protein bands of prefrontal cortex. (D) SYN positive products (a–c) were brownish yellow granules located in the neuropil. Scale bar = 50 μm. The OD of SYN was shown in a statistical graph (d). The datas were expressed as the mean ± SD (n = 3). *p < 0.05, **p < 0.01 and ***P < 0.001, vs. the RA group. #p < 0.05, ##p < 0.01 and ###P < 0.001, compared to CIH group. Full-length blots/gels are presented in Supplementary Figure A.

Mentions: SYN expression in the CIH group was significantly lower compared to RA group. The SYN expression in PCA treated rats is high, and its IOD values were significantly higher compared to CIH group both in hippocampus and prefrontal cortex (Fig. 5A,C). Immunohistochemical (IHC) staining for SYN showed brownish yellow granules that were located in the neuropil, but not in the nucleus and perikaryon (Fig. 5B a–c). In addition, the staining was located in neuropil of prefrontal cortex (Fig. 5D a–c). The expression of the SYN protein in hippocampus and prefrontal cortex by IHC method was consistent with the SYN protein bands detected by WB among the different groups. The OD values of hippocampus were 0.199 ± 0.034, 0.085 ± 0.014 and 0.134 ± 0.019, respectively, in the RA group, CIH group and CIH+PCA group (Fig. 5B d). The OD values of prefrontal cortex were 0.201 ± 0.021, 0.142 ± 0.014 and 0.174 ± 0.025 (Fig. 5D d). Results demonstrate that CIH results in a down-regulation of the protein levels of SYN, and PCA treatment significantly increases the level of SYN protein in hippocampus (Fig. 5B d) and prefrontal cortex (Fig. 5D d).


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

Yin X, Zhang X, Lv C, Li C, Yu Y, Wang X, Han F - Sci Rep (2015)

(A) Western blotting analysis revealed SYN protein bands of hippocampus. (B) SYN positive products (a–c) were brownish yellow granules located in the neuropil. Scale bar = 50 μm. The OD of SYN was shown in a statistical graph (d). The results were expressed as the mean ± SD (n = 3). **P < 0.05 vs. RA group, #P < 0.05 vs. CIH group. (C) Western blotting analysis revealed SYN protein bands of prefrontal cortex. (D) SYN positive products (a–c) were brownish yellow granules located in the neuropil. Scale bar = 50 μm. The OD of SYN was shown in a statistical graph (d). The datas were expressed as the mean ± SD (n = 3). *p < 0.05, **p < 0.01 and ***P < 0.001, vs. the RA group. #p < 0.05, ##p < 0.01 and ###P < 0.001, compared to CIH group. Full-length blots/gels are presented in Supplementary Figure A.
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Related In: Results  -  Collection

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f5: (A) Western blotting analysis revealed SYN protein bands of hippocampus. (B) SYN positive products (a–c) were brownish yellow granules located in the neuropil. Scale bar = 50 μm. The OD of SYN was shown in a statistical graph (d). The results were expressed as the mean ± SD (n = 3). **P < 0.05 vs. RA group, #P < 0.05 vs. CIH group. (C) Western blotting analysis revealed SYN protein bands of prefrontal cortex. (D) SYN positive products (a–c) were brownish yellow granules located in the neuropil. Scale bar = 50 μm. The OD of SYN was shown in a statistical graph (d). The datas were expressed as the mean ± SD (n = 3). *p < 0.05, **p < 0.01 and ***P < 0.001, vs. the RA group. #p < 0.05, ##p < 0.01 and ###P < 0.001, compared to CIH group. Full-length blots/gels are presented in Supplementary Figure A.
Mentions: SYN expression in the CIH group was significantly lower compared to RA group. The SYN expression in PCA treated rats is high, and its IOD values were significantly higher compared to CIH group both in hippocampus and prefrontal cortex (Fig. 5A,C). Immunohistochemical (IHC) staining for SYN showed brownish yellow granules that were located in the neuropil, but not in the nucleus and perikaryon (Fig. 5B a–c). In addition, the staining was located in neuropil of prefrontal cortex (Fig. 5D a–c). The expression of the SYN protein in hippocampus and prefrontal cortex by IHC method was consistent with the SYN protein bands detected by WB among the different groups. The OD values of hippocampus were 0.199 ± 0.034, 0.085 ± 0.014 and 0.134 ± 0.019, respectively, in the RA group, CIH group and CIH+PCA group (Fig. 5B d). The OD values of prefrontal cortex were 0.201 ± 0.021, 0.142 ± 0.014 and 0.174 ± 0.025 (Fig. 5D d). Results demonstrate that CIH results in a down-regulation of the protein levels of SYN, and PCA treatment significantly increases the level of SYN protein in hippocampus (Fig. 5B d) and prefrontal cortex (Fig. 5D d).

Bottom Line: The effects of PCA on oxidative stress, apoptosis, and brain IL-1β levels were investigated.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.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, Shandong, 264003, China.

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.

No MeSH data available.


Related in: MedlinePlus