Movement Disorder in Copper Toxicity Rat Model: Role of Inflammation and Apoptosis in the Corpus Striatum

Neurotox Res. 2020 Apr;37(4):904-912. doi: 10.1007/s12640-019-00140-9. Epub 2019 Dec 6.

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.

Keywords: Copper toxicity; Corpus striatum; Movement disorder; Oxidative stress; Spontaneous locomotor activity; Wilson disease.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Copper Sulfate / toxicity*
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Corpus Striatum / pathology*
  • Disease Models, Animal*
  • Inflammation / chemically induced
  • Inflammation / metabolism
  • Inflammation / pathology
  • Locomotion / drug effects
  • Locomotion / physiology
  • Male
  • Movement Disorders / metabolism
  • Movement Disorders / pathology*
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology*
  • Rats
  • Rats, Wistar

Substances

  • Copper Sulfate