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Abstract
The present study was undertaken to explore the potential of erythropoietin in memory deficits of mice. Memory impairment was produced by scopolamine (0.5 mg/kg, i.p.) and intracerebroventricular streptozotocin (i.c.v STZ, 3 mg/kg, 10 μl, 1st and 3rd day) in separate groups of animals. Morris water-maze test was employed to assess learning and memory. The levels of brain thio-barbituric acid reactive species (TBARS) and reduced glutathione (GSH) were estimated to assess degree of oxidative stress. Brain acetylcholinesterase enzyme (AChE) activity was also measured. Scopolamine/streptozotocin administration induced significant impairment of learning and memory in mice as indicated by marked decrease in Morris water-maze performance. Scopolamine/streptozotocin administration also produced a significant enhancement of brain AChE activity and brain oxidative stress (an increase in TBARS and a decrease in GSH) levels. Treatment of erythropoietin (500 and 1,000 IU/Kg i.p.) significantly reversed scopolamine- as well as streptozotocin-induced learning and memory deficits along with attenuation of those-induced rise in brain AChE activity and brain oxidative stress levels. It may be concluded that erythropoietin exerts a beneficial effect in memory deficits of mice possibly through its multiple actions including potential anti-oxidative effect.
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Fig. 1.
Effect of erythropoietin on scopolamine and streptozotocin induced memory impairments using Morris water-maze. ACSF-C: artificial cerebrospinal fluid-control; SCO-C: scopolamine-control; EPO-L and H: erythropoietin (low and high); STZ: streptozotocin. Each group (n=7) represents mean±standard errors of means Two-way ANOVA followed by Bonferonni's post hoc test. F (3, 24)=6.455, p<0.0001 for evaluating the difference in time spent in various quadrants; F (9, 60)=26.231, p<0.001 for evaluating the effect of treatment on difference in time spent in target quadrant. ap<0.05 Vs time spent in other quadrants in control group, bp< 0.05 Vs time spent in Target Quadrant (TSTQ) of control, cp<0.05 Vs TSTQ of scopolamine group, dp<0.05 Vs TSTQ of ACSF group, ep<0.05 Vs TSTQ of STZ group.
Fig. 2.
Effect of erythropoietin on scopolamine/streptozotocin-induced changes in brain AChE activity. ACSF-C: artificial cerebrospinal fluid-control; SCO-C: scopolamine-control; EPO-L and H: erythropoietin (low and high); STZ: streptozotocin. Each group (n=7) represents mean±standard errors of means. One-way ANOVA followed by Tukey's multiple range test; F (9, 60)=15.851, p<0.001. ap<0.05 Vs control group, bp<0.05 Vs scopolamine, cp<0.05 Vs ACSF control, dp<0.05 Vs STZ.
Fig. 3.
Effect of erythropoietin on scopolamine/streptozotocin-induced changes in brain thio-barbituric acid reactive species (TBARS) levels. ACSF-C: artificial cerebrospinal fluid-control; SCO-C: scopolamine-control; EPO-L and H: erythropoietin (low and high); STZ: streptozotocin. Each group (n=7) represents mean±standard errors of means. One-way ANOVA followed by Tukey's multiple range test; F (9, 60)=10.721, p<0.001. ap<0.05 Vs control group, bp<0.05 Vs scopolamine, cp<0.05 Vs ACSF control, dp<0.05 Vs STZ.
Fig. 4.
Effect of erythropoietin on scopolamine/streptozotocin-induced changes in brain reduced glutathione (GSH) levels. ACSF-C: artificial cerebrospinal fluid-control; SCO-C: scopolamine-control; EPO-L and H: erythropoietin (low and high); STZ: streptozotocin. Each group (n=7) represents mean±standard errors of means. One-way ANOVA followed by Tukey's multiple range test; F (9, 60)=16.522, p<0.001. ap<0.05 Vs control group, bp<0.05 Vs scopolamine, cp<0.05 Vs ACSF control, dp<0.05 Vs STZ.
Table 1.
Effect of erythropoietin on scopolamine/streptozotocin-induced changes in escape latency time (ELT) using Morris water-maze
| Sr. No. | Group | Dose | Day 1 ELT (sec) | Day 4 ELT (sec) |
|---|---|---|---|---|
| I | Control | 10 ml/kg, i.p. | 95.5±4.11 | 38.5±1.04a |
| II | ACSF control | 25 mg/ml, 10 μl, i.c.v | 97.2±3.64 | 40.2±1.40a |
| III | scopolamine | 0.5 mg/kg, i.p. | 92.8±1.01 | 66±0.69b |
| IV | EPO-L | 500 IU/kg, i.p. | 94.1±1.5 | 39.4±0.97a |
| V | EPO-H | 1000 IU/kg, i.p. | 95.1±1.47 | 41.1±1.4a |
| VI | EPO-L+scopolamine | 500 IU/kg, i.p.+0.5 mg/kg, i.p. | 95.4±1.96 | 45.1±0.76c |
| VII | EPO-H+scopolamine | 1000 IU/kg i.p.+0.5 mg/kg, i.p. | 97.7±1.04 | 40±1c |
| VIII | STZ | 3 mg/kg, 10 μl, i.c.v | 99.1±1.10 | 75.5±1.41d |
| IX | STZ+EPO-L | 3 mg/kg, 10 μl, i.c.v+500 IU/kg, i.p. | 96.5±1.67 | 49.1±1.03e |
| X | STZ+EPO-H | 3 mg/kg, 10 μl, i.c.v+1,000 IU/kg, i.p. | 97.5±0.78 | 42.5±0.89e |
ACSF-C: artificial cerebrospinal fluid-control; EPO-L and H: erythropoietin (low and high); STZ: streptozotocin; ELT: escape latency time. Each group (n=7) represents mean±standard errors of means. Two-way ANOVA followed by Bonferonni's post hoc test. F (3, 24)=11. 100, p<0.001 for evaluating the effect of days and F (9, 60)=50.740, p<0.001 for evaluating the effect of treatment on ELT,
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