title: Iron administration prevents BDNF decrease and depressive-like behavior following chronic stress.
abstract: Pro-inflammatory cytokines play important roles in responses to stresses and affect iron metabolism. Iron is essential for survival of hippocampus neurons and plays a role in depression. Noting the close causal effect relation between stress and depression, in this experimental study we investigated the influence of iron on stress-induced depression. Rats were exposed to chronic mild stress and were treated with three different iron doses (9, 12, and 20mg/kg) three times a week for four weeks with an iron chelator in the first and third week. Serum interleukin-6 (enzyme-linked immune sorbent assay), hippocampus iron content (atomic absorption spectrometry), brain-derived neurotrophic factor (BDNF) gene expression (real-time polymerase chain reaction), CA1 pyramidal cell count (Nissl method) and a behavioral test (forced swimming test) were evaluated. In both the stressed and stressed plus iron groups, hippocampus cell counts were lower than in the control group (non-stressed). The use of deferiprone in the stressed groups markedly prevented neuronal loss. In stressed rats, the iron content of the hippocampus was higher than in the control group (P<0.001). Moreover, in the stressed group with moderate iron administration (12 mg/kg), there was a significant elevation of BDNF expression (P<0.05) and decreased immobility behavior time (P<0.05). These results indicate that high doses of iron in stressful situations augment neuronal degeneration and loss, possibly by iron accumulation. Deferiprone as an iron chelator could reverse this effect. During chronic mild stress, cerebrospinal fluid possibly reduces the iron content and may result in reduction of monoamines being involved in mood regulation. Iron administration in a moderate dose can increase these neurotransmitters and BDNF expression.
authors.affiliation: Physiology Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Sara
authors.initials: S
authors.lastname: Mehrpouya
authors.affiliation: Physiology Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran. Electronic address: arezoonahavandi1999@gmail.com.
authors.forename: Arezo
authors.initials: A
authors.lastname: Nahavandi
authors.affiliation: Physiology Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Khojasteh
authors.affiliation: Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Mansoureh
authors.initials: M
authors.lastname: Soleimani
authors.affiliation: Physiology Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ahmadi
authors.affiliation: Department of Biotechnology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Mahmood
authors.initials: M
authors.lastname: Barati
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002908:Chronic Disease; D003863:Depression / Q000188:drug therapy* / Q000209:etiology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007501:Iron / Q000008:administration & dosage* / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000150:complications*; D013550:Swimming / Q000523:psychology; D013997:Time Factors; D014131:Trace Elements / Q000008:administration & dosage*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D015850:Interleukin-6; D014131:Trace Elements; D007501:Iron
keywords: Brain-derived neurotrophic factor; Hippocampus; Iron; Stress-induced depression