• Changes in motor performance and AMPA gene expression in the cerebellum of male rats during copper toxicity and treatment with vit C
  • Zahra Nobakht Mobaraki,1,* Homeira Hatami Nemati,2 Nazli Khajehnasiri,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 Biological Sciences, Faculty of Basic Sciences, Higher Education Institute of Rab-Rashid, Tabriz, Iran.


  • Introduction: Copper is an essential transition metal that participates in the regulation of brain physiology, being a key structural component of various proteins and a co-factor for enzymes that are critical for brain function, including enzymes involved in antioxidant defense and cellular respiration. More recently, some reports have described the effect of copper at the synaptic level, where it modulates complex parameters such as Long Term Potentiation (LTP) and receptor pharmacology. Synaptic receptors may be targets for copper. α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) is a major type of ionotropic glutamate receptors involved in synaptic transmission. However, excessive activity of these receptors can be cytotoxic and thus their function must be precisely controlled. Indeed, it has been observed that copper inhibits AMPAergic neurotransmission. Thus, suggesting that copper has an acute modulatory role on the AMPA receptor in neurotransmission. There is evidence about up regulation of AMPA receptor expression and cell damage. We analyze the motor activity and changes in AMPA gene expression during neurotoxicity process of copper sulfate and evaluate the results of treatments using vitamin C in the cerebellum of male rats. Copper is critical for the Central Nervous System (CNS) development and function. In particular, different studies have shown the effect of copper at brain synapses, where it inhibits Long Term Potentiation (LTP) and receptor pharmacology. Paradoxically, according to recent studies copper is required for a normal LTP response. Copper is released at the synaptic cleft, where it blocks glutamate receptors, which explain its blocking effects on excitatory neurotransmission.
  • Methods: In this experimental study, 24 male Wister rats (250-300 gr) were randomly divided into 4 groups of 6 (n=6 in each). Control (normal saline), copper sulfate (10 mg/kg; i.p), vitamin C (160 mg/ kg; i.p), copper sulfate + vitamin C (160 mg/kg; i.p) for 10 days. On days 1, 5 and 10, coordination of rats' movements was assessed using the rotarod test 20 minutes after injection. After receiving treatments, the animals were decapitated and their cerebellum were removed and the expression of AMPA gene assayed using RT-PCR Technique. One-way ANOVA and post-hoc Tukey test were used for data analyzing.
  • Results: Data analysis showed that the mean duration of resistance and remaining on the rotarod wheel in copper sulfate group was not significantly different from the control group (p> 0.05). While the mean duration significantly increased for the group of vitamin C compared to the control group (p <0.001). The mean duration significantly increased for the group of copper sulfate + vitamin C compared to the control group (p<0.05). The mean duration significantly decrease for the group of copper sulfate compared to the vitamin C group (p<0/001). The mean duration significantly decrease for the group of copper sulfate compared to the copper sulfate + vitamin C group (p<0.05). The mean duration significantly increased for the group of vitamin C compared to the copper sulfate + vitamin C group (p<0.05). The expression level of AMPA gene in vitamin C and copper sulfate+ vitamin C group was not significantly different from the control group (p> 0.05). The AMPA gene expression increased in the copper sulfate group compared to the control group (p<0.001).The expression level of AMPA gene in copper sulfate was not significantly different from vitamin C group (p> 0.05). The AMPA gene expression increased in the copper sulfate group compared to the copper sulfate + vitamin (p<0.01).The expression level of AMPA gene in vitamin C and copper sulfate + vitamin C group was not significantly different from the control group (p> 0.05).
  • Conclusion: Our results indicate that copper increase the levels of AMPA gene expression and overload disturbed neuromuscular coordination. Also we think that the AMPA receptor may play a role in cerebellar injury caused by copper overload.
  • Keywords: Copper toxicity, vit C, NMDA gene expression, locomotor activity, rotarod test.