Neuroprotective effect of melatonin in mice with toxic cuprizone model of demyelination and possible pathways of its realization

Home/2018, Vol. 6, No. 2/Neuroprotective effect of melatonin in mice with toxic cuprizone model of demyelination and possible pathways of its realization

Cell and Organ Transplantology. 2018; 6(2):145-151.
DOI: 10.22494/cot.v6i2.87

Neuroprotective effect of melatonin in mice with toxic cuprizone model of demyelination and possible pathways of its realization

Labunets I. F., Rodnichenko A. E., Melnyk N. O., Utko N. O.
State Institute of Genetic and Regenerative Medicine National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine


The search for tools that increase the effectiveness of cell therapy of demyelinating pathology is relevant. They may be preparations that affect the pathogenetic factors of this pathology, in particular, the pineal hormone melatonin.
The purpose of the study is to evaluate the involvement of immune system and antioxidant defense in the implementation of the protective effects of melatonin on morphofunctional disorders in the central nervous system induced by neurotoxin cuprizone.
Materials and methods. The toxic demyelination model was induced on 129/Sv mice at the age of 3-5 months by adding cuprizone to food for 3 weeks. Since the 7th day of cuprizone administration, melatonin was  injected intraperitoneally at 6 p.m. daily, at a dose of 1 mg/kg. In the brain of mice, the proportion of CD3+, Nestin+ cells and phagocytic macrophages, the content of malondialdehyde and the activity of antioxidant enzymes was determined. Blood serum was tested for thymic hormone thymulin levels. In the animals, we evaluated the structure of the brain and spinal cord neurons by Nissl staining of histological sections as well as analyzed behavioural reactions in the «open field» test.
Results. In the brain of the mice receiving cuprizone, the proportion of CD3+ and Nestin+ cells, active macrophages and malondialdehyde content increased, glutathione peroxidase and glutathione reductase levels decreased. In the brain and spinal cord of the mice with a cuprizone diet, the proportion of altered neurons increased, and motor and emotional activity decreased. The administration of melatonin results in a decrease in the relative number of CD3+ cells, active macrophages and malondialdehyde content, increased activity of glutathione peroxidase, glutathione reductase and level of thymulin. In such mice, the proportion of unchanged neurons increases as the number of Nestin+ cells decreases and behavioural responses are also improved.
Conclusions. The neuroprotective effect of melatonin in demyelinating pathology is realized through the factors of the immune system and oxidative stress. The results may be useful in the development of new biotechnological approaches to the treatment of demyelinating pathology, in particular, multiple sclerosis.

Key words:  cuprizone; melatonin; neuron; T-lymphocytes; brain macrophages; thymulin; antioxidant enzymes

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Labunets I, Rodnichenko A, Melnyk N, Utko N. Neuroprotective effect of melatonin in mice with toxic cuprizone model of demyelination and possible pathways of its realization. Cell and Organ Transplantology. 2018; 6(2):145-151. doi:10.22494/cot.v6i2.87

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