Abstract
The pattern of copper (Cu) toxicity in humans is similar to Wilson disease, and they have movement disorders and frequent involvement of corpus striatum. The extent of cell deaths in corpus striatum may be the basis of movement disorder and may be confirmed in the experimental study. To evaluate the extent of apoptosis and glial activation in corpus striatum following Cu toxicity in a rat model, and correlate these with spontaneous locomotor activity (SLA), six male Wistar rats were fed normal saline (group I) and another six were fed copper sulfate 100 mg/kgBWt/daily orally (group II). At 1 month, neurobehavioral studies including SLA, rotarod, and grip strength were done. Corpus striatum was removed and was subjected to glial fibrillary acidic protein (GFAP) and caspase-3 immunohistochemistry. The concentration of tissue Cu, total antioxidant capacity (TAC), glutathione (GSH), malondialdehyde (MDA), and glutamate were measured. Group II rats had higher expression of caspase-3 (Mean ± SEM 32.67 ± 1.46 vs 4.47 ± 1.08; p < 0.01) and GFAP (41.81 ± 1.68 vs 31.82 ± 1.27; p < 0.01) compared with group I. Neurobehavioral studies revealed reduced total distance traveled, time moving, the number of rearing, latency to fall on the rotarod, grip strength, and increased resting time compared with group I. The expression of GFAP and caspase-3 correlated with SLA parameters, tissue Cu, GSH, MDA, TAC, and glutamate levels. The impaired locomotor activity in Cu toxicity rats is due to apoptotic and inflammatory-mediated cell death in the corpus striatum because of Cu-mediated oxidative stress and excitotoxicity.
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Abbreviations
- Cu:
-
Copper
- kgBWt:
-
Kg body weight
- LEC:
-
Long-Evans Cinnamon
- WD:
-
Wilson disease
- GSH:
-
Glutathione
- TAC:
-
Total antioxidant capacity
- MDA:
-
Malondialdehyde
- LPO:
-
Lipid peroxidation
- SLA:
-
Spontaneous locomotor activity
- TX mice:
-
Toxic milk mice
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Acknowledgments
We gratefully acknowledge the help of Dr. R.C. Murthy, CSIR, Indian Institute of Toxicology Research, Lucknow, for providing facilities for Cu estimation.
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Supplementary Fig 3A
Regression curve showing a correlation between the percentage of Caspase-3 positive cells with neurobehavioral parameters. On Spontaneous Locomotor Activity study, caspase-3 had an inverse correlation with (A1) total distance traveled, (A3) time moving and (A4) number of rearing; whereas had a positive correlation with (A2) time resting. Percentage of Caspase-3 positive cells also had an inverse correlation with (A5) grip strength and (A6) latency to fall time on the rotarod. (PNG 362 kb)
Supplementary Fig 3B
Regression curve showing a correlation of percentage of Glial Fibrillary Acidic Protein (GFAP) positive cells with neurobehavioral parameters. On the Spontaneous Locomotor Activity study, GFAP had an inverse correlation with (B1) total distance traveled, (B3) time moving and (B4) number of rearing; whereas had a positive correlation with (B2) time resting. Percentage of GFAP-positive cells also had an inverse correlation with (B5) grip strength and (B6) latency to fall time on the rotarod. (PNG 339 kb)
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Kalita, J., Kumar, V., Misra, U.K. et al. Movement Disorder in Copper Toxicity Rat Model: Role of Inflammation and Apoptosis in the Corpus Striatum. Neurotox Res 37, 904–912 (2020). https://doi.org/10.1007/s12640-019-00140-9
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DOI: https://doi.org/10.1007/s12640-019-00140-9