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Research Article

Metformin pretreatment enhanced learning and memory in cerebral forebrain ischaemia: the role of the AMPK/BDNF/P70SK signalling pathway

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Pages 2211-2219 | Received 22 Aug 2015, Accepted 01 Feb 2016, Published online: 09 Mar 2016

Figures & data

Figure 1. Outline scheme of experimental designs. Rats were pretreated with metformin over 14 d and on days 13 and 14, the 4VO surgery was done. On the day 17, the behavioural tests for passive avoidance task and neurological scores were evaluated and rats were scarified for molecular measurements (CCA, common carotid arteries; VA, vertebral arteries; CC, compound C).

Figure 1. Outline scheme of experimental designs. Rats were pretreated with metformin over 14 d and on days 13 and 14, the 4VO surgery was done. On the day 17, the behavioural tests for passive avoidance task and neurological scores were evaluated and rats were scarified for molecular measurements (CCA, common carotid arteries; VA, vertebral arteries; CC, compound C).

Table. 1. Metformin improves neurological scores in the global cerebral ischaemia/reperfusion models.

Figure 2. Evaluated effects of administration of metformin and CC on step through latency in ischemic rats. (A) Latency time to the dark chamber was detected for 5 min and expressed as seconds. (B) Time spent in dark chamber was recorded over 5 min. Bars indicate the mean ± SEM. ***p< 0.001 versus the sham group, ##p< 0.01, ###p< 0.001 versus the I/R group. $p< 0.05 versus the met + I/R group. Met, metformin (200 mg/kg); CC, compound C; I/R, ischaemia/reperfusion.

Figure 2. Evaluated effects of administration of metformin and CC on step through latency in ischemic rats. (A) Latency time to the dark chamber was detected for 5 min and expressed as seconds. (B) Time spent in dark chamber was recorded over 5 min. Bars indicate the mean ± SEM. ***p< 0.001 versus the sham group, ##p< 0.01, ###p< 0.001 versus the I/R group. $p< 0.05 versus the met + I/R group. Met, metformin (200 mg/kg); CC, compound C; I/R, ischaemia/reperfusion.

Figure 3. Western blot analysis to measure the effect of metformin pretreatment on the mature BDNF levels in the hippocampus. (A) Western blots for pro-BDNF are shown. (B) The density of pro-BDNF bands was measured and their ratio was calculated. Bars indicate the mean ± SEM. ***p< 0.001 versus the sham group, ###p< 0.01, ###p< 0.001 versus the I/R group, $$$p < 0.001 versus the met + I/R group. Met, metformin (200 mg/kg); CC, compound C; I/R, ischaemia/reperfusion.

Figure 3. Western blot analysis to measure the effect of metformin pretreatment on the mature BDNF levels in the hippocampus. (A) Western blots for pro-BDNF are shown. (B) The density of pro-BDNF bands was measured and their ratio was calculated. Bars indicate the mean ± SEM. ***p< 0.001 versus the sham group, ###p< 0.01, ###p< 0.001 versus the I/R group, $$$p < 0.001 versus the met + I/R group. Met, metformin (200 mg/kg); CC, compound C; I/R, ischaemia/reperfusion.

Figure 4. The western blotting analysis was used to measure the effect of pretreatment with metformin on the phosphorylated P70S6K, total P70S6K levels in the hippocampus. (A) Western blots for phosphorylated P70S6K, total P70S6K are shown. (B) The density of phosphorylated P70S6K to total P70S6K bands was measured and their ratio was calculated. Bars indicate the mean ± SEM. ***p< 0.001 versus the sham group, ###p< 0.001 versus the I/R group, $$p < 0.01 versus the met + I/R group. Met, metformin (200 mg/kg); CC, compound C; I/R, ischaemia/reperfusion.

Figure 4. The western blotting analysis was used to measure the effect of pretreatment with metformin on the phosphorylated P70S6K, total P70S6K levels in the hippocampus. (A) Western blots for phosphorylated P70S6K, total P70S6K are shown. (B) The density of phosphorylated P70S6K to total P70S6K bands was measured and their ratio was calculated. Bars indicate the mean ± SEM. ***p< 0.001 versus the sham group, ###p< 0.001 versus the I/R group, $$p < 0.01 versus the met + I/R group. Met, metformin (200 mg/kg); CC, compound C; I/R, ischaemia/reperfusion.

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