Pretreatment with Human Lactoferrin Had a Positive Effect on the Dynamics of Mouse Nigrostriatal System Recovery after Acute MPTP Exposure

SIMPLE SUMMARY: Parkinson’s disease (PD) is the progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in substantia nigra and depletion of dopamine in the striatum. Many efforts are now focused on the search for agents that can weaken PD progression, prevent further neurodegeneration, and restore the degenerated dopaminergic neurons. The present study explores the effects of lactoferrin (a multifunctional protein from the transferrin family) in the MPTP-treated mice as the model of dopaminergic neuron loss. MPTP is a neurotoxin that upon systemic administration selectively destroys dopaminergic neurons of the nigrostriatal system inducing number of the symptoms observed in idiopathic PD. Our data suggest that pretreatment with human lactoferrin significantly alleviated MPTP toxicity. This was manifested in improved motor functions and exploratory behavior, partial recovery of the number of tyrosine hydroxylase (TH)-positive cells in the substantia nigra, and TH-positive fibers in the striatum. The results of this work elucidate the role of lactoferrin in protective and compensatory mechanisms and provide the basis for potential use of this protein in the treatment of human neurodegenerative diseases. ABSTRACT: We studied the effect of human lactoferrin (hLf) on degenerative changes in the nigrostriatal system and associated behavioral deficits in the animal model of Parkinson disease. Nigrostriatal dopaminergic injury was induced by single administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 40 mg/kg) to five-month-old C57Bl/6 mice. Behavioral disturbances were assessed in the open field and rotarod tests and by the stride length analysis. Structural deficits were assessed by the counts of tyrosine hydroxylase (TH)-immunoreactive neurons in the substantia nigra and optical density (OD) of TH-immunolabeled fibers in the striatum. Acute MPTP treatment induced long-term behavioral deficit and degenerative changes in the nigrostriatal system. Pretreatment with hLf prevented body weight loss and promoted recovery of motor functions and exploratory behavior. Importantly, OD of TH-positive fibers in the striatum of mice treated with hLf almost returned to normal, and the number of TH-positive cells in the substantia nigra significantly increased on day 28. These results indicate that hLf produces a neuroprotective effect and probably stimulates neuroregeneration under conditions of MPTP toxicity in our model. A relationship between behavioral deficits and nigrostriatal system disturbances at delayed terms after MPTP administration was found.