Erythropoietin prevents the effect of chronic restraint stress on the number of hippocampal CA3c dendritic terminalsrelation to expression of genes involved in synaptic plasticity, angiogenesis, inflammation, and oxidative stress in male rats

被引:12
作者
Aalling, Nadia [1 ,2 ]
Hageman, Ida [1 ,2 ]
Miskowiak, Kamilla [3 ,4 ]
Orlowski, Dariusz [5 ]
Wegener, Gregers [6 ,7 ]
Wortwein, Gitta [1 ,2 ,8 ]
机构
[1] Rigshosp, Psychiat Ctr Copenhagen, Lab Neuropsychiat, Copenhagen, Denmark
[2] Univ Copenhagen, Fac Hlth & Med Sci, Dept Neurosci & Pharmacol, Copenhagen, Denmark
[3] Copenhagen Univ Hosp, Rigshosp, Psychiat Ctr Copenhagen, Copenhagen Affect Disorder Res Ctr, Copenhagen, Denmark
[4] Univ Copenhagen, Dept Psychol, Copenhagen, Denmark
[5] Univ Aarhus, Dept Clin Med, Ctr Expt Neurosci Cense, Aarhus, Denmark
[6] Univ Aarhus, Dept Clin Med, Translat Neuropsychiat Unit, Aarhus, Denmark
[7] North West Univ, Ctr Excellence Pharmaceut Sci, Potchefstroom Campus, Potchefstroom, South Africa
[8] Univ Copenhagen, Fac Hlth & Med Sci, Dept Publ Hlth, Copenhagen, Denmark
关键词
depression; animal model; allostatic load; novelty-suppressed feeding; RRID:SCR_002865; TRAUMATIC BRAIN-INJURY; APICAL DENDRITES; GLUCOCORTICOID-RECEPTOR; ADULT NEUROGENESIS; PYRAMIDAL NEURONS; INDUCED ATROPHY; MOOD DISORDERS; DEPRESSION; BEHAVIOR; HYPOXIA;
D O I
10.1002/jnr.24107
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Stress-induced allostatic load affects a variety of biological processes including synaptic plasticity, angiogenesis, oxidative stress, and inflammation in the brain, especially in the hippocampus. Erythropoietin (EPO) is a pleiotropic cytokine that has shown promising neuroprotective effects. Recombinant human EPO is currently highlighted as a new candidate treatment for cognitive impairment in neuropsychiatric disorders. Because EPO enhances synaptic plasticity, attenuates oxidative stress, and inhibits generation of proinflammatory cytokines, EPO may be able to modulate the effects of stress-induced allostatic load at the molecular level. The aim of this study was therefore to investigate how EPO and repeated restraint stress, separately and combined, influence (i) behavior in the novelty-suppressed feeding test of depression/anxiety-related behavior; (ii) mRNA levels of genes encoding proteins involved in synaptic plasticity, angiogenesis, oxidative stress, and inflammation; and (iii) remodeling of the dendritic structure of the CA3c area of the hippocampus in male rats. As expected, chronic restraint stress lowered the number of CA3c apical dendritic terminals, and EPO treatment reversed this effect. Interestingly, these effects seemed to be mechanistically distinct, as stress and EPO had differential effects on gene expression. While chronic restraint stress lowered the expression of spinophilin, tumor necrosis factor , and heat shock protein 72, EPO increased expression of hypoxia-inducible factor-2 and lowered the expression of vascular endothelial growth factor in hippocampus. These findings indicate that the effects of treatment with EPO follow different molecular pathways and do not directly counteract the effects of stress in the hippocampus.
引用
收藏
页码:103 / 116
页数:14
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