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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

DCX immunoflourescent labelling of the dentate gyrus region of the hippocampus at 20X magnification.EPO treatment (black bars) increased DCX+ neuron counts relative to saline treatment (hatched bars). The bottom photomicrographs depict representative images from the treatment groups: A. Saline, B. EPO, C. Saline + Stress and D. EPO + Stress. Data are expressed as mean ± SEM (n = 8/group) *p < 0.01, **p < 0.001.
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pone-0072813-g004: DCX immunoflourescent labelling of the dentate gyrus region of the hippocampus at 20X magnification.EPO treatment (black bars) increased DCX+ neuron counts relative to saline treatment (hatched bars). The bottom photomicrographs depict representative images from the treatment groups: A. Saline, B. EPO, C. Saline + Stress and D. EPO + Stress. Data are expressed as mean ± SEM (n = 8/group) *p < 0.01, **p < 0.001.

Mentions: There were no main effects of [p = 0.413] or interactions involving behavioural testing and stress condition [p = 0.521] or behavioural testing and injection treatment [p = 0.200] on the number of DCX+ hippocampal neurons (Figure 4). There was also no significant three-way interaction between behavioural testing, stress condition and injection treatment [p = 0.904]. In the absence of any Stressor x EPO interactions [p = 0.118], there were significant main effects for both the stressor and EPO treatments. Specifically, the stressor induced a modest but significant reduction in DCX+ neurons F(1,24)= 28.62, [p = 0.009], whereas EPO treatment increased the number of DCX+ hippocampal neurons F(1,24) = 28.97, [p = 0.001], It is noteworthy that in the presence of the stressor, EPO increased DCX+ counts over and above that observed among saline treated animals (albeit to a lesser degree than that observed in the absence of the stressful challenge).


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)

DCX immunoflourescent labelling of the dentate gyrus region of the hippocampus at 20X magnification.EPO treatment (black bars) increased DCX+ neuron counts relative to saline treatment (hatched bars). The bottom photomicrographs depict representative images from the treatment groups: A. Saline, B. EPO, C. Saline + Stress and D. EPO + Stress. Data are expressed as mean ± SEM (n = 8/group) *p < 0.01, **p < 0.001.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0072813-g004: DCX immunoflourescent labelling of the dentate gyrus region of the hippocampus at 20X magnification.EPO treatment (black bars) increased DCX+ neuron counts relative to saline treatment (hatched bars). The bottom photomicrographs depict representative images from the treatment groups: A. Saline, B. EPO, C. Saline + Stress and D. EPO + Stress. Data are expressed as mean ± SEM (n = 8/group) *p < 0.01, **p < 0.001.
Mentions: There were no main effects of [p = 0.413] or interactions involving behavioural testing and stress condition [p = 0.521] or behavioural testing and injection treatment [p = 0.200] on the number of DCX+ hippocampal neurons (Figure 4). There was also no significant three-way interaction between behavioural testing, stress condition and injection treatment [p = 0.904]. In the absence of any Stressor x EPO interactions [p = 0.118], there were significant main effects for both the stressor and EPO treatments. Specifically, the stressor induced a modest but significant reduction in DCX+ neurons F(1,24)= 28.62, [p = 0.009], whereas EPO treatment increased the number of DCX+ hippocampal neurons F(1,24) = 28.97, [p = 0.001], It is noteworthy that in the presence of the stressor, EPO increased DCX+ counts over and above that observed among saline treated animals (albeit to a lesser degree than that observed in the absence of the stressful challenge).

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