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.

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Despite the well-established fact that maternal care plays a pivotal role in the offspring development, little is known about the effects of disruption of maternal care early in life on the development of this behavior in the offspring. Using brief repeated maternal separation (45 min/day on postnatal Days 3–6), which represents a model of early life stress, we found behavioral changes in adult female mice offspring. The decrease in home cage exploratory behavior (both pup-directed and nonpup-directed) was revealed later in adulthood without changes in maternal care level. Maternal separation coupled with pain exposure caused by subcutaneous saline injection procedure had a cumulative resulting effect, which was manifested in the decreased level of nursing associated with licking-grooming in adult females. The behavioral changes found in adult female offspring could be triggered by identified changes in the behavior of their mothers, while alterations of the level of histone H3 acetylation in the neonatal brain were not detected. Histone deacetylase inhibitor sodium valproate was used in order to study the possibility of preventing the effects of early life stress through involvement of epigenetic mechanisms. Despite the increase in the level of histone H3 acetylation in the neonatal brain caused by valproate, its behavioral effects were barely detectable. These effects were reflected in prevention of the reduction of nursing associated with licking-grooming induced by maternal separation, accompanied by pain exposure. The data are discussed in terms of the possible application to the studies of mechanisms underlying long-term effects of human early life trauma.

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We studied the effects of human lactoferrin (hLf), a multifunctional protein from the transferrin family, on integral (survival, lifespan during the experiment, body weight, behavior, subfractional compositions of blood serum) and systemic (hemoglobin level, leukocyte number, differential leukocyte count, histological structure of the liver and spleen) parameters of the body in mice after acute gamma irradiation in a sublethal dose. The experiments were performed on male C57BL/6 mice. The mice in the experimental groups were exposed to whole-body gamma radiation in a dose of 7.5 Gy from a 60Co source. Immediately after irradiation and 24 h after it, some animals received an intraperitoneal injection of hLf (4 mg/mouse). Single or repeated administration of hLf had a positive pleiotropic effect on irradiated animals: animal survival increased from 28% to 78%, and the mean life expectancy during the experiment (30 days) increased from 16 to 26 days. A compensatory effect of hLf on radiation-induced body weight loss, changes in homeostasis parameters, and a protective effect on the structural organization of the spleen were demonstrated. These data indicate that Lf has potential as a means of early therapy after radiation exposure.