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Antidepressant-like effects of erythropoietin: a focus on behavioural and hippocampal processes.

Osborn M, Rustom N, Clarke M, Litteljohn D, Rudyk C, Anisman H, Hayley S - PLoS ONE (2013)

Bottom Line: Furthermore, EPO promoted adult hippocampal neurogenesis, an important feature of effective antidepressants.These data are consistent with previous findings showing that the mTOR pathway and its neurogenic and synaptogenic effects might mediate the behavioral consequences of antidepressant agents.Our findings further highlight EPO as a possible adjunct treatment for affective disorders, as well as other stressor associated disorders of impaired neuroplasticity.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, Carleton University, Ottawa, Ontario, Canada.

ABSTRACT
Depression is a chronic and debilitating condition with a significant degree of relapse and treatment resistance that could stem, at least in part, from disturbances of neuroplasticity. This has led to an increased focus on treatment strategies that target brain derived neurotrophic factor (BDNF), synaptic plasticity and adult neurogenesis. In the current study we aimed to assess whether erythropoietin (EPO) would have antidepressant-like effects given its already established pro-trophic actions. In particular, we assessed whether EPO would diminish the deleterious effects of a social stressor in mice. Indeed, EPO induced anxiolytic and antidepressant-like responses in a forced swim test, open field, elevated-plus maze, and a novelty test, and appeared to blunt some of the negative behavioural effects of a social stressor. Furthermore, EPO promoted adult hippocampal neurogenesis, an important feature of effective antidepressants. Finally, a separate study using the mTOR inhibitor rapamycin revealed that antagonizing this pathway prevented the impact of EPO upon forced swim performance. These data are consistent with previous findings showing that the mTOR pathway and its neurogenic and synaptogenic effects might mediate the behavioral consequences of antidepressant agents. Our findings further highlight EPO as a possible adjunct treatment for affective disorders, as well as other stressor associated disorders of impaired neuroplasticity.

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Related in: MedlinePlus

Time spent mobile, in seconds, in the forced swim test (FST).Data are expressed as mean ± SEM (n = 8/group). EPO (black bars) clearly reduced FST immobility relative to the saline treatment (hatched bars). This effect was apparent whether mice were exposed to the stressor regimen or not. *p < 0.001 relative to saline-treated controls.
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pone-0072813-g001: Time spent mobile, in seconds, in the forced swim test (FST).Data are expressed as mean ± SEM (n = 8/group). EPO (black bars) clearly reduced FST immobility relative to the saline treatment (hatched bars). This effect was apparent whether mice were exposed to the stressor regimen or not. *p < 0.001 relative to saline-treated controls.

Mentions: There was no significant main effect of the stressor condition [p = 0.967], nor was there a significant interaction between the stressor condition and injection type on immobility time in the FST [p = 0.162]. However, the ANOVA revealed that EPO significantly reduced immobility in the forced swim test, irrespective of whether or not mice had been exposed to the stressor F(1,28) = 2.07, [p = 0.001] (Figure 1).


Antidepressant-like effects of erythropoietin: a focus on behavioural and hippocampal processes.

Osborn M, Rustom N, Clarke M, Litteljohn D, Rudyk C, Anisman H, Hayley S - PLoS ONE (2013)

Time spent mobile, in seconds, in the forced swim test (FST).Data are expressed as mean ± SEM (n = 8/group). EPO (black bars) clearly reduced FST immobility relative to the saline treatment (hatched bars). This effect was apparent whether mice were exposed to the stressor regimen or not. *p < 0.001 relative to saline-treated controls.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3760922&req=5

pone-0072813-g001: Time spent mobile, in seconds, in the forced swim test (FST).Data are expressed as mean ± SEM (n = 8/group). EPO (black bars) clearly reduced FST immobility relative to the saline treatment (hatched bars). This effect was apparent whether mice were exposed to the stressor regimen or not. *p < 0.001 relative to saline-treated controls.
Mentions: There was no significant main effect of the stressor condition [p = 0.967], nor was there a significant interaction between the stressor condition and injection type on immobility time in the FST [p = 0.162]. However, the ANOVA revealed that EPO significantly reduced immobility in the forced swim test, irrespective of whether or not mice had been exposed to the stressor F(1,28) = 2.07, [p = 0.001] (Figure 1).

Bottom Line: Furthermore, EPO promoted adult hippocampal neurogenesis, an important feature of effective antidepressants.These data are consistent with previous findings showing that the mTOR pathway and its neurogenic and synaptogenic effects might mediate the behavioral consequences of antidepressant agents.Our findings further highlight EPO as a possible adjunct treatment for affective disorders, as well as other stressor associated disorders of impaired neuroplasticity.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, Carleton University, Ottawa, Ontario, Canada.

ABSTRACT
Depression is a chronic and debilitating condition with a significant degree of relapse and treatment resistance that could stem, at least in part, from disturbances of neuroplasticity. This has led to an increased focus on treatment strategies that target brain derived neurotrophic factor (BDNF), synaptic plasticity and adult neurogenesis. In the current study we aimed to assess whether erythropoietin (EPO) would have antidepressant-like effects given its already established pro-trophic actions. In particular, we assessed whether EPO would diminish the deleterious effects of a social stressor in mice. Indeed, EPO induced anxiolytic and antidepressant-like responses in a forced swim test, open field, elevated-plus maze, and a novelty test, and appeared to blunt some of the negative behavioural effects of a social stressor. Furthermore, EPO promoted adult hippocampal neurogenesis, an important feature of effective antidepressants. Finally, a separate study using the mTOR inhibitor rapamycin revealed that antagonizing this pathway prevented the impact of EPO upon forced swim performance. These data are consistent with previous findings showing that the mTOR pathway and its neurogenic and synaptogenic effects might mediate the behavioral consequences of antidepressant agents. Our findings further highlight EPO as a possible adjunct treatment for affective disorders, as well as other stressor associated disorders of impaired neuroplasticity.

Show MeSH
Related in: MedlinePlus