Iron administration prevents BDNF decrease and depressive-like behavior following chronic stress

• Moderate dose of iron prevents BDNF decrease following chronic stress.
• Moderate dose of iron prevents depressive-like behavior following chronic stress.
• Deferiprone administration can decrease cell destruction following chronic stress.
• IL-6 level which was higher in stressful condition is not altered in existence of iron or deferiprone.

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 20 mg/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.