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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,B) Chronic intermittent hypoxia protocol. (C) Step-through passive avoidance test. We measured latency until rats first entered into the dark chamber. *P < 0.05 indicates a significant difference from the CIH group.(D, a) Pathlength of rats during training in Morris water maze. PCA administration decreases the pathlength in rats trained in Morris water maze. (D, b) Latency of rats during training in Morris water maze. PCA administration deceases the latency. (D, c) Number of times rats cross the platform position during probe trail. (D, d) Time. spent in the quadrants during probe trail. The fourth quadrant (Q4) of the Morris water maze had the submerged platform. All data points are mean ± SD. * denotes p < 0.05 when compared to RA group and # denotes p < 0.05 when compared to CIH group. n = 15.
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f1: (A,B) Chronic intermittent hypoxia protocol. (C) Step-through passive avoidance test. We measured latency until rats first entered into the dark chamber. *P < 0.05 indicates a significant difference from the CIH group.(D, a) Pathlength of rats during training in Morris water maze. PCA administration decreases the pathlength in rats trained in Morris water maze. (D, b) Latency of rats during training in Morris water maze. PCA administration deceases the latency. (D, c) Number of times rats cross the platform position during probe trail. (D, d) Time. spent in the quadrants during probe trail. The fourth quadrant (Q4) of the Morris water maze had the submerged platform. All data points are mean ± SD. * denotes p < 0.05 when compared to RA group and # denotes p < 0.05 when compared to CIH group. n = 15.

Mentions: In step-through passive avoidance test, latency time, relative to the motor and explorative activity of rats, showed no statistically significant differences among groups, demonstrating that animals behave the same during the acquisition trial (Fig. 1C). In the retention trial, a change in step-through latency time indicates the consolidation of the reinforced stimuli in the memory of rats. CIH significantly decreased latency compared to the RA group (36.1 ± 10.3 vs. 102.5 ± 27.9, p < 0.05). On the contrary, PCA treated rats showed significantly higher latency compared to the CIH group (114.7 ± 16.1 vs. 36.1 ± 10.3, p < 0.05) on day 2. Briefly, PCA exhibited significant protective effects on learning/memory ability of rats compared to the CIH groups (Fig. 1C).


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,B) Chronic intermittent hypoxia protocol. (C) Step-through passive avoidance test. We measured latency until rats first entered into the dark chamber. *P < 0.05 indicates a significant difference from the CIH group.(D, a) Pathlength of rats during training in Morris water maze. PCA administration decreases the pathlength in rats trained in Morris water maze. (D, b) Latency of rats during training in Morris water maze. PCA administration deceases the latency. (D, c) Number of times rats cross the platform position during probe trail. (D, d) Time. spent in the quadrants during probe trail. The fourth quadrant (Q4) of the Morris water maze had the submerged platform. All data points are mean ± SD. * denotes p < 0.05 when compared to RA group and # denotes p < 0.05 when compared to CIH group. n = 15.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4588513&req=5

f1: (A,B) Chronic intermittent hypoxia protocol. (C) Step-through passive avoidance test. We measured latency until rats first entered into the dark chamber. *P < 0.05 indicates a significant difference from the CIH group.(D, a) Pathlength of rats during training in Morris water maze. PCA administration decreases the pathlength in rats trained in Morris water maze. (D, b) Latency of rats during training in Morris water maze. PCA administration deceases the latency. (D, c) Number of times rats cross the platform position during probe trail. (D, d) Time. spent in the quadrants during probe trail. The fourth quadrant (Q4) of the Morris water maze had the submerged platform. All data points are mean ± SD. * denotes p < 0.05 when compared to RA group and # denotes p < 0.05 when compared to CIH group. n = 15.
Mentions: In step-through passive avoidance test, latency time, relative to the motor and explorative activity of rats, showed no statistically significant differences among groups, demonstrating that animals behave the same during the acquisition trial (Fig. 1C). In the retention trial, a change in step-through latency time indicates the consolidation of the reinforced stimuli in the memory of rats. CIH significantly decreased latency compared to the RA group (36.1 ± 10.3 vs. 102.5 ± 27.9, p < 0.05). On the contrary, PCA treated rats showed significantly higher latency compared to the CIH group (114.7 ± 16.1 vs. 36.1 ± 10.3, p < 0.05) on day 2. Briefly, PCA exhibited significant protective effects on learning/memory ability of rats compared to the CIH groups (Fig. 1C).

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