Korean J Physiol Pharmacol.  2010 Oct;14(5):345-352. 10.4196/kjpp.2010.14.5.345.

Effects of Erythropoietin on Memory Deficits and Brain Oxidative Stress in the Mouse Models of Dementia

• Kumar R
• Jaggi AS
• Singh N

• KMID: 2071704
• DOI: http://doi.org/10.4196/kjpp.2010.14.5.345

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 microliter, 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.

Keyword

Erythropoietin; Memory; Scopolamine; Streptozotocin; Morris water-maze

MeSH Terms

Acetylcholinesterase
Animals
Brain
Dementia
Erythropoietin
Glutathione
Learning
Memory
Memory Disorders
Mice
Oxidative Stress
Scopolamine Hydrobromide
Streptozocin
Thiobarbituric Acid Reactive Substances
Acetylcholinesterase
Erythropoietin
Glutathione
Scopolamine Hydrobromide
Streptozocin
Thiobarbituric Acid Reactive Substances

Figure

• 

  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.

Reference

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