Cuprizone-Induced Disorders of Central Nervous System Neurons, Behavioral Reactions, Brain Activity of Macrophages and Antioxidant Enzymes in the Mice of Different Ages: Role Leukemia Inhibitory Factor in Their Improvement
Objective: The present work aimed at studying neuroprotective effects of recombinant human leukemia inhibitory factor (rhLIF) on mice of different ages with cuprizone model of demyelination.
Methods:In the 129/Sv mice at 3-5 and 16-17 months of age we assessed (a) motor and emotional activity in the “open field” test and (b) activity of brain antioxidant enzymes and macrophages capable to phagocytosis of latex beads. After staining histological sections of the brain and spinal cord toluidin blue we determined the percentage of neurons with unmodified, moderate and severe structural changes. Cuprizone was fed daily for 3 weeks. RhLIF was injected after 7-days cuprizone diet, one administration daily, 50 µg/kg.
Results: In the cuprizone-treated mice of both age groups, the percentage of neurons with severe changes in the brain and spinal cord were increased. In the young and aged animals receiving cuprizone and rhLIF the amounts of neurones with destructive changes were reduced, being less pronounced in aged mice. Cuprizone decreased the amounts of crossed squares and faecal boluses in the mice of both age groups. RhLIF restored emotional activity in these mice, but the increase of motor activity was observed only in young mice. In the brain of cuprizone-treated mice of both age groups the activity of catalase and glutathione peroxidase (GP) inhibits; the changes were more pronounced in the aged mice. Positive effects of rhLIF on GP activity were seen only in the young mice. The percentage of active macrophages was increased in cuprizone-treated mice of both age groups. Decrease of amount and activity of macrophages after injections of the rhLIF was observed only in the aged animals.
Conclusion: LIF may be a perspective neuroprotective drug in multiple sclerosis. The efficiency of LIF in multiple sclerosis can be raised if the data about its role in aging are taken into account.