• Alteration of NT4 gene expression and depression- like behaviors during copper toxicity in the brain of rats under vitamin C treatment
  • Sama Radbin,1,* Homeira Hatami,2 Hatam Ahmadi,3
    1. Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
    2. Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
    3. Department of Basic Sciences, Farhangian University, Tehran, Iran


  • Introduction: Copper is one of the essential elements of the body. The amount of copper in human brain tissue is about 3.1 mg/g. In mice, it is 5.5 and in rats, it is 0.1 mg/g. But excess amounts of copper can damage the brain by causing oxidative stress. Excessive increase or decrease in copper causes neurodegenerative diseases. To counteract this effects, the use of antioxidants is recommended. Ascorbic acid (vitamin C) is antioxidant and it can stand against the effects of oxidative stress. Neurotrophin-4 (NT-4) is a member of a family of neurotrophic factors, the neurotrophins that control survival and differentiation of vertebrate neurons. Neurotropic factor 4 (NT4) is involved in different neural process. Studies show that neurotrophin 4 is a protective and survival factor against neurotoxicity. So in this study, we evaluated the NT4 gene expression alterations and locomotor activity in rats following copper toxicity and treatment with vit C.
  • Methods: Twenty four male Wistar rats were randomly assigned into four groups (n=6). Control, copper sulfate (10 mg/kg; i.p), vitamin C (100 mg/kg; i.p), copper sulfate +vitamin C (100mg/kg; i.p) doses for 10 days. The exploratory behavior and depression- like behaviors of animals were assessed by open field test on the first, fifth and tenth days of the injection. After receiving treatments, the animals were decapitated and their cerebral hemispheres were removed and the expression of NT4 gene assayed using RT- PCR. One-way ANOVA were used for data analyzing.
  • Results: Data analyzing showed that the duration of presence in the central part of the open field device in copper sulfate group and vitamin C group and copper sulfate + vitamin C group, significantly decreased compared to the control group (p<0.001). There is no significant difference between copper sulfate receiving group and vitamin C group and copper sulfate + vitamin C group (p>0.05). And there is no significant difference between vitamin C group and copper sulfate + vitamin C group (p>0.05). The frequency of entry of the group receiving copper sulfate and vitamin C group and copper sulfate + vitamin C group in the central part, significantly decreased compared to the control group (p<0.001). There is no significant difference between copper sulfate receiving group and vitamin C group and copper sulfate + vitamin C group (p>0.05). And there is no significant difference between vitamin C group and copper sulfate + vitamin C group (p>0.05). The NT4 gene expression decreased in the copper sulfate group and vitamin C group and copper sulfate + vitamin C group compared to the control group (p<0.001). There is no significant difference between copper sulfate receiving group and vitamin C group and copper sulfate + vitamin C group (p>0.05). And there is no significant difference between vitamin C group and copper sulfate + vitamin C group (p>0.05).
  • Conclusion: Behavioral data analyzing showed copper toxicity induced depression like behaviors in rats in a way rats the rats did not want to explore and search the central part of open field device. Most of animals crawled in the corners of open field device. Interestingly vit C did not improved their behaviors. Also molecular data analyzing showed that the level of NT4 gene expression decreased during copper toxicity and vit C treatment was not able to approach it to the control level. Good coordination between behavioral data analyzing and molecular data analyzing was seen.
  • Keywords: Copper sulfate, Vit C, Neurotrophin-4 gene expression