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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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Sevoflurane induced apoptosis of cells in the hippocampus of aged rats.Apoptosis was examined by the TUNEL method. Upper: Photomicrographs of TUNEL-positive cells. (a) Control group. (b) Sevoflurane group. (c) Number of TUNEL-positive cells in each group. Data are presented as mean ± SD. *P<0.05, vs control group.
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pone-0057870-g005: Sevoflurane induced apoptosis of cells in the hippocampus of aged rats.Apoptosis was examined by the TUNEL method. Upper: Photomicrographs of TUNEL-positive cells. (a) Control group. (b) Sevoflurane group. (c) Number of TUNEL-positive cells in each group. Data are presented as mean ± SD. *P<0.05, vs control group.

Mentions: TUNEL is a common method for detecting DNA fragmentation that results from apoptotic signaling cascades. TUNEL immunohistochemistry revealed a distinctive pattern of nuclear staining (Figure 5). The number of TUNEL positive cells was significantly higher in the sevoflurane group compared to the control group in the hippocampal CA1 and DG region (Figure 5, P<0.05).


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

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

Sevoflurane induced apoptosis of cells in the hippocampus of aged rats.Apoptosis was examined by the TUNEL method. Upper: Photomicrographs of TUNEL-positive cells. (a) Control group. (b) Sevoflurane group. (c) Number of TUNEL-positive cells in each group. Data are presented as mean ± SD. *P<0.05, vs control group.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0057870-g005: Sevoflurane induced apoptosis of cells in the hippocampus of aged rats.Apoptosis was examined by the TUNEL method. Upper: Photomicrographs of TUNEL-positive cells. (a) Control group. (b) Sevoflurane group. (c) Number of TUNEL-positive cells in each group. Data are presented as mean ± SD. *P<0.05, vs control group.
Mentions: TUNEL is a common method for detecting DNA fragmentation that results from apoptotic signaling cascades. TUNEL immunohistochemistry revealed a distinctive pattern of nuclear staining (Figure 5). The number of TUNEL positive cells was significantly higher in the sevoflurane group compared to the control group in the hippocampal CA1 and DG region (Figure 5, P<0.05).

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