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Protective Effect of RNase on Unilateral Nephrectomy-Induced Postoperative Cognitive Dysfunction in Aged Mice.

Chen C, Cai J, Zhang S, Gan L, Dong Y, Zhu T, Ma G, Li T, Zhang X, Li Q, Cheng X, Wu C, Yang J, Zuo Y, Liu J - PLoS ONE (2015)

Bottom Line: We found that perioperative administration of RNase: 1) attenuated unilateral nephrectomy-induced cognitive impairment at day 3 after surgery; 2) reduced the hippocampal cytokines mRNA production and serum cytokines protein production at day 1 and day 7 (for MCP-1) after surgery, and; 3) inhibited hippocampal apoptosis as indicated by cleaved caspase-3 western blot and TUNEL staining at day 1 after surgery.In addition, a trend decrease of total serum RNA levels was detected in the RNase treated group after surgery compared with the untreated group.Further, our protocol of RNase administration had no impact on the arterial blood gas analysis right after surgery, kidney function and mortality rate at the observed days postoperatively.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

ABSTRACT
Postoperative cognitive dysfunction (POCD) is a common complication after surgery, especially for elderly patients. Administration of RNase has been reported to exhibit neuroprotective effects in acute stroke. However, the potential role of RNase on POCD is unknown. Therefore, we sought to investigate whether RNase treatment could mitigate unilateral nephrectomy induced-cognitive deficit in aged mice. In the present study, twelve-month-old mice were administered RNase or an equal amount of normal saline perioperatively. All mice underwent Morris Water Maze (MWM) training 3 times per day for 7 days to acclimatize them to the water maze before surgical operation, and testing on days 1, 3 and 7 after surgery. We found that perioperative administration of RNase: 1) attenuated unilateral nephrectomy-induced cognitive impairment at day 3 after surgery; 2) reduced the hippocampal cytokines mRNA production and serum cytokines protein production at day 1 and day 7 (for MCP-1) after surgery, and; 3) inhibited hippocampal apoptosis as indicated by cleaved caspase-3 western blot and TUNEL staining at day 1 after surgery. In addition, a trend decrease of total serum RNA levels was detected in the RNase treated group after surgery compared with the untreated group. Further, our protocol of RNase administration had no impact on the arterial blood gas analysis right after surgery, kidney function and mortality rate at the observed days postoperatively. In conclusion, perioperative RNase treatment attenuated unilateral nephrectomy-induced cognitive impairment in aged mice.

No MeSH data available.


Related in: MedlinePlus

RNase treatment reduced cognitive impairment induced by unilateral nephrectomy surgery in aged mice.The MWM was used for the training of spatial memory formation in aged mice for 7 days before experiments and followed by the postoperative testing of reversal learning for 7 days. A, Escape latency during the experiments. B, Percentage of time spent in the target quadrant during the experiments. C, Swimming path length during the experiments. D, Swimming speed during the experiments. E, The probe trial test at day 3 and day 7 after surgery. F, Representative swim paths for S-R and S-P group at day 3 after surgery. The above data are shown as mean ± SEM; n = 10 for training; n = 8 for testing. *P<0.05 v.s. S-S group, #P<0.05 v.s. S-R group. S-S, sham surgery plus placebo; S-P, surgery plus placebo; S-R, surgery plus RNase.
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pone.0134307.g002: RNase treatment reduced cognitive impairment induced by unilateral nephrectomy surgery in aged mice.The MWM was used for the training of spatial memory formation in aged mice for 7 days before experiments and followed by the postoperative testing of reversal learning for 7 days. A, Escape latency during the experiments. B, Percentage of time spent in the target quadrant during the experiments. C, Swimming path length during the experiments. D, Swimming speed during the experiments. E, The probe trial test at day 3 and day 7 after surgery. F, Representative swim paths for S-R and S-P group at day 3 after surgery. The above data are shown as mean ± SEM; n = 10 for training; n = 8 for testing. *P<0.05 v.s. S-S group, #P<0.05 v.s. S-R group. S-S, sham surgery plus placebo; S-P, surgery plus placebo; S-R, surgery plus RNase.

Mentions: Assessment of hippocampal-dependent learning and memory by MWM in all treatment groups at day 3 postoperatively demonstrated a statistically significant reduction in memory retrieval in S-P group compared to the S-S group, as evidenced by escape latency, path length, and percentage of time spent in target quadrant respectively (Fig 2A–2C), suggesting that unilateral nephrectomy induced a significant cognitive impairment in aged mice, therefore emulating POCD. The S-P group had similar swimming speed as that of the S-S group either pre or postoperatively (Fig 2D), implying that surgical operation per se had no impact on exercise capacity of the mice. Importantly, RNase treatment led to significantly enhanced cognitive function, compared with untreated surgical group, as demonstrated by escape latency (23.01 ± 5.15 vs. 43.67 ± 7.23, #P< 0.05) (Fig 2A), path length (333.20 ± 60.60 vs. 636.33 ± 89.72, #P<0.05) (Fig 2B), and percentage time spent in target quadrant (27.08 ± 2.84% vs. 24.21 ± 1.33%, #P<0.05) (Fig 2C), indicating that RNase treatment can attenuate POCD induced by unilateral nephrectomy in aged mice. Likewise, there was no difference in swimming speed either pre or postoperatively between S-R group and S-P group (Fig 2D). Additionally, a probe test was conducted at day 3 and day 7 after surgery to test whether the mice had learned and could recall the spatial location of the hidden platform. The percentage of time spent in the quadrant with the previously located hidden platform was significantly less in the S-P group undergoing probe tests (29.00 ± 1.88% and 36.12 ± 0.80%) when compared with the S-S group (39.48 ± 3.06% and 42.00 ± 2.11%) on day 3 and day 7 after surgery, respectively (Fig 2E, P<0.05). The S-R group undergoing probe tests had a significantly higher percentage of time spent in the target quadrant compared to that of the S-P group at day 3 after surgery (37.66 ± 2.28% vs. 29.00 ± 1.88%, #P< 0.05) (Fig 2E). Additionally, RNase treatment had no impact on the sham group (data not shown). Taken together, the above results revealed that unilateral nephrectomy induced a significant cognitive impairment, which could be attenuated by perioperative RNase treatment.


Protective Effect of RNase on Unilateral Nephrectomy-Induced Postoperative Cognitive Dysfunction in Aged Mice.

Chen C, Cai J, Zhang S, Gan L, Dong Y, Zhu T, Ma G, Li T, Zhang X, Li Q, Cheng X, Wu C, Yang J, Zuo Y, Liu J - PLoS ONE (2015)

RNase treatment reduced cognitive impairment induced by unilateral nephrectomy surgery in aged mice.The MWM was used for the training of spatial memory formation in aged mice for 7 days before experiments and followed by the postoperative testing of reversal learning for 7 days. A, Escape latency during the experiments. B, Percentage of time spent in the target quadrant during the experiments. C, Swimming path length during the experiments. D, Swimming speed during the experiments. E, The probe trial test at day 3 and day 7 after surgery. F, Representative swim paths for S-R and S-P group at day 3 after surgery. The above data are shown as mean ± SEM; n = 10 for training; n = 8 for testing. *P<0.05 v.s. S-S group, #P<0.05 v.s. S-R group. S-S, sham surgery plus placebo; S-P, surgery plus placebo; S-R, surgery plus RNase.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4520469&req=5

pone.0134307.g002: RNase treatment reduced cognitive impairment induced by unilateral nephrectomy surgery in aged mice.The MWM was used for the training of spatial memory formation in aged mice for 7 days before experiments and followed by the postoperative testing of reversal learning for 7 days. A, Escape latency during the experiments. B, Percentage of time spent in the target quadrant during the experiments. C, Swimming path length during the experiments. D, Swimming speed during the experiments. E, The probe trial test at day 3 and day 7 after surgery. F, Representative swim paths for S-R and S-P group at day 3 after surgery. The above data are shown as mean ± SEM; n = 10 for training; n = 8 for testing. *P<0.05 v.s. S-S group, #P<0.05 v.s. S-R group. S-S, sham surgery plus placebo; S-P, surgery plus placebo; S-R, surgery plus RNase.
Mentions: Assessment of hippocampal-dependent learning and memory by MWM in all treatment groups at day 3 postoperatively demonstrated a statistically significant reduction in memory retrieval in S-P group compared to the S-S group, as evidenced by escape latency, path length, and percentage of time spent in target quadrant respectively (Fig 2A–2C), suggesting that unilateral nephrectomy induced a significant cognitive impairment in aged mice, therefore emulating POCD. The S-P group had similar swimming speed as that of the S-S group either pre or postoperatively (Fig 2D), implying that surgical operation per se had no impact on exercise capacity of the mice. Importantly, RNase treatment led to significantly enhanced cognitive function, compared with untreated surgical group, as demonstrated by escape latency (23.01 ± 5.15 vs. 43.67 ± 7.23, #P< 0.05) (Fig 2A), path length (333.20 ± 60.60 vs. 636.33 ± 89.72, #P<0.05) (Fig 2B), and percentage time spent in target quadrant (27.08 ± 2.84% vs. 24.21 ± 1.33%, #P<0.05) (Fig 2C), indicating that RNase treatment can attenuate POCD induced by unilateral nephrectomy in aged mice. Likewise, there was no difference in swimming speed either pre or postoperatively between S-R group and S-P group (Fig 2D). Additionally, a probe test was conducted at day 3 and day 7 after surgery to test whether the mice had learned and could recall the spatial location of the hidden platform. The percentage of time spent in the quadrant with the previously located hidden platform was significantly less in the S-P group undergoing probe tests (29.00 ± 1.88% and 36.12 ± 0.80%) when compared with the S-S group (39.48 ± 3.06% and 42.00 ± 2.11%) on day 3 and day 7 after surgery, respectively (Fig 2E, P<0.05). The S-R group undergoing probe tests had a significantly higher percentage of time spent in the target quadrant compared to that of the S-P group at day 3 after surgery (37.66 ± 2.28% vs. 29.00 ± 1.88%, #P< 0.05) (Fig 2E). Additionally, RNase treatment had no impact on the sham group (data not shown). Taken together, the above results revealed that unilateral nephrectomy induced a significant cognitive impairment, which could be attenuated by perioperative RNase treatment.

Bottom Line: We found that perioperative administration of RNase: 1) attenuated unilateral nephrectomy-induced cognitive impairment at day 3 after surgery; 2) reduced the hippocampal cytokines mRNA production and serum cytokines protein production at day 1 and day 7 (for MCP-1) after surgery, and; 3) inhibited hippocampal apoptosis as indicated by cleaved caspase-3 western blot and TUNEL staining at day 1 after surgery.In addition, a trend decrease of total serum RNA levels was detected in the RNase treated group after surgery compared with the untreated group.Further, our protocol of RNase administration had no impact on the arterial blood gas analysis right after surgery, kidney function and mortality rate at the observed days postoperatively.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

ABSTRACT
Postoperative cognitive dysfunction (POCD) is a common complication after surgery, especially for elderly patients. Administration of RNase has been reported to exhibit neuroprotective effects in acute stroke. However, the potential role of RNase on POCD is unknown. Therefore, we sought to investigate whether RNase treatment could mitigate unilateral nephrectomy induced-cognitive deficit in aged mice. In the present study, twelve-month-old mice were administered RNase or an equal amount of normal saline perioperatively. All mice underwent Morris Water Maze (MWM) training 3 times per day for 7 days to acclimatize them to the water maze before surgical operation, and testing on days 1, 3 and 7 after surgery. We found that perioperative administration of RNase: 1) attenuated unilateral nephrectomy-induced cognitive impairment at day 3 after surgery; 2) reduced the hippocampal cytokines mRNA production and serum cytokines protein production at day 1 and day 7 (for MCP-1) after surgery, and; 3) inhibited hippocampal apoptosis as indicated by cleaved caspase-3 western blot and TUNEL staining at day 1 after surgery. In addition, a trend decrease of total serum RNA levels was detected in the RNase treated group after surgery compared with the untreated group. Further, our protocol of RNase administration had no impact on the arterial blood gas analysis right after surgery, kidney function and mortality rate at the observed days postoperatively. In conclusion, perioperative RNase treatment attenuated unilateral nephrectomy-induced cognitive impairment in aged mice.

No MeSH data available.


Related in: MedlinePlus