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Sevoflurane induces endoplasmic reticulum stress mediated apoptosis in hippocampal neurons of aging rats.

Chen G, Gong M, Yan M, Zhang X - PLoS ONE (2013)

Bottom Line: The ultrastructure of the hippocampus was observed by transmission electron microscopy (TEM).The expressions of C/EBP homologous protein (CHOP) and caspase-12 in the hippocampus were observed by immunohistochemistry and real-time PCR analysis.The present results suggested that the long time exposure of sevoflurane could induce neuronal degeneration and cognitive impairment in aging rats.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

ABSTRACT
Elderly patients are more likely to suffer from postoperative memory impairment for volatile anesthetics could induce aging neurons degeneration and apoptosis while the mechanism was still elusive. Therefore we hypothesized that ER stress mediated hippocampal neurons apoptosis might play an important role in the mechanism of sevoflurane-induced cognitive impairment in aged rats. Thirty 18-month-old male Sprague-Dawley rats were divided into two groups: the sham anesthesia group (exposure to simply humidified 30-50% O2 balanced by N2 in an acrylic anesthetizing chamber for 5 hours) and the sevoflurane anesthesia group (received 2% sevoflurane in the same humidified mixed air in an identical chamber for the same time). Spatial memory of rats was assayed by the Morris water maze test. The ultrastructure of the hippocampus was observed by transmission electron microscopy (TEM). The expressions of C/EBP homologous protein (CHOP) and caspase-12 in the hippocampus were observed by immunohistochemistry and real-time PCR analysis. The apoptosis neurons were also assessed by TUNEL assay. The Morris water maze test showed that sevoflurane anesthesia induced spatial memory impairment in aging rats (P<0.05). The apoptotic neurons were condensed and had clumped chromatin with fragmentation of the nuclear membrane, verifying apoptotic degeneration in the sevoflurane group rats by TEM observation. The expressions of CHOP and caspase-12 increased, and the number of TUNEL positive cells of the hippocampus also increased in the sevoflurane group rats (P<0.05). The present results suggested that the long time exposure of sevoflurane could induce neuronal degeneration and cognitive impairment in aging rats. The ER stress mediated neurons apoptosis may play a role in the sevoflurane-induced memory impairment in aging rats.

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The effect of sevoflurane exposure on the memory and learning ability by Morris Water Maze testing.(a) Effects of sevoflurane on escape latency to find the hidden platform. The latency to find the hidden platform was significantly higher in sevoflurane-exposed rats than control rats. (b) The number of times that the rat crossed over the previous platform site within 120 s. (c) The time the rats stay in the target quadrant. Data are presented as mean ± SD. *P<0.05; **P<0.01, vs control group.
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pone-0057870-g001: The effect of sevoflurane exposure on the memory and learning ability by Morris Water Maze testing.(a) Effects of sevoflurane on escape latency to find the hidden platform. The latency to find the hidden platform was significantly higher in sevoflurane-exposed rats than control rats. (b) The number of times that the rat crossed over the previous platform site within 120 s. (c) The time the rats stay in the target quadrant. Data are presented as mean ± SD. *P<0.05; **P<0.01, vs control group.

Mentions: To evaluate the effect of sevoflurane exposure on the memory and learning ability, we subjected the rats to Morris Water Maze testing. As shown in Figure 1 a, all rats had a tendency of reduced latency to find the hidden platform as training progressed, indicating that the animals were learning from the day by day practice. However, we found that sevoflurane anesthesia had a significant effect on spatial orientation in the navigation task because it impaired the performance of the sevoflurane group. On the training day 1, 2, 3, and 4, the sevoflurane group rats showed significantly longer latency to locate the hidden platform than the control group (Figure 1 a), indicating significantly impairment in learning and memory functions after sevoflurane exposure. To check memory retrieval, the times that the animal crossed the platform position during the probe trial was analyzed. As shown in Figure 1 b, the number of times crossing over the previous platform site in the rats of the sevoflurane group were fewer than that of control group. Also the rats of the sevoflurane group spent less percentage of time swimming (25.3±2.6%) in the probe quadrant as compared with the control animals (34.1±3.5%) (P<0.05). These data suggested that the sevoflurane exposure could cause impairment in memory.


Sevoflurane induces endoplasmic reticulum stress mediated apoptosis in hippocampal neurons of aging rats.

Chen G, Gong M, Yan M, Zhang X - PLoS ONE (2013)

The effect of sevoflurane exposure on the memory and learning ability by Morris Water Maze testing.(a) Effects of sevoflurane on escape latency to find the hidden platform. The latency to find the hidden platform was significantly higher in sevoflurane-exposed rats than control rats. (b) The number of times that the rat crossed over the previous platform site within 120 s. (c) The time the rats stay in the target quadrant. Data are presented as mean ± SD. *P<0.05; **P<0.01, vs control group.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585271&req=5

pone-0057870-g001: The effect of sevoflurane exposure on the memory and learning ability by Morris Water Maze testing.(a) Effects of sevoflurane on escape latency to find the hidden platform. The latency to find the hidden platform was significantly higher in sevoflurane-exposed rats than control rats. (b) The number of times that the rat crossed over the previous platform site within 120 s. (c) The time the rats stay in the target quadrant. Data are presented as mean ± SD. *P<0.05; **P<0.01, vs control group.
Mentions: To evaluate the effect of sevoflurane exposure on the memory and learning ability, we subjected the rats to Morris Water Maze testing. As shown in Figure 1 a, all rats had a tendency of reduced latency to find the hidden platform as training progressed, indicating that the animals were learning from the day by day practice. However, we found that sevoflurane anesthesia had a significant effect on spatial orientation in the navigation task because it impaired the performance of the sevoflurane group. On the training day 1, 2, 3, and 4, the sevoflurane group rats showed significantly longer latency to locate the hidden platform than the control group (Figure 1 a), indicating significantly impairment in learning and memory functions after sevoflurane exposure. To check memory retrieval, the times that the animal crossed the platform position during the probe trial was analyzed. As shown in Figure 1 b, the number of times crossing over the previous platform site in the rats of the sevoflurane group were fewer than that of control group. Also the rats of the sevoflurane group spent less percentage of time swimming (25.3±2.6%) in the probe quadrant as compared with the control animals (34.1±3.5%) (P<0.05). These data suggested that the sevoflurane exposure could cause impairment in memory.

Bottom Line: The ultrastructure of the hippocampus was observed by transmission electron microscopy (TEM).The expressions of C/EBP homologous protein (CHOP) and caspase-12 in the hippocampus were observed by immunohistochemistry and real-time PCR analysis.The present results suggested that the long time exposure of sevoflurane could induce neuronal degeneration and cognitive impairment in aging rats.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

ABSTRACT
Elderly patients are more likely to suffer from postoperative memory impairment for volatile anesthetics could induce aging neurons degeneration and apoptosis while the mechanism was still elusive. Therefore we hypothesized that ER stress mediated hippocampal neurons apoptosis might play an important role in the mechanism of sevoflurane-induced cognitive impairment in aged rats. Thirty 18-month-old male Sprague-Dawley rats were divided into two groups: the sham anesthesia group (exposure to simply humidified 30-50% O2 balanced by N2 in an acrylic anesthetizing chamber for 5 hours) and the sevoflurane anesthesia group (received 2% sevoflurane in the same humidified mixed air in an identical chamber for the same time). Spatial memory of rats was assayed by the Morris water maze test. The ultrastructure of the hippocampus was observed by transmission electron microscopy (TEM). The expressions of C/EBP homologous protein (CHOP) and caspase-12 in the hippocampus were observed by immunohistochemistry and real-time PCR analysis. The apoptosis neurons were also assessed by TUNEL assay. The Morris water maze test showed that sevoflurane anesthesia induced spatial memory impairment in aging rats (P<0.05). The apoptotic neurons were condensed and had clumped chromatin with fragmentation of the nuclear membrane, verifying apoptotic degeneration in the sevoflurane group rats by TEM observation. The expressions of CHOP and caspase-12 increased, and the number of TUNEL positive cells of the hippocampus also increased in the sevoflurane group rats (P<0.05). The present results suggested that the long time exposure of sevoflurane could induce neuronal degeneration and cognitive impairment in aging rats. The ER stress mediated neurons apoptosis may play a role in the sevoflurane-induced memory impairment in aging rats.

Show MeSH
Related in: MedlinePlus