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

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.

Lactoferrin Protects against Methamphetamine Toxicity by Modulating Autophagy and Mitochondrial Status

“…This alternative hypothesis is consistent with data provided in the present and previous studies. In fact, LF protects DA neurons against METH-induced neurodegeneration (present study) and that induced by the parkinsonian neurotoxin MPTP [36][37][38].…”

“…It is remarkable that, LF appears to protect neurons from the very same disorders featuring endogenous overexpression of LF. This is the case of dementia [30][31][32] and experimental Parkinsonism [33][34][35][36][37][38].…”

A Review on Lactoferrin and Central Nervous System Diseases

“…The function of circulating Lf in the brain may be to protect these susceptible neurons rather than to cause iron accumulation and neuronal death [ 100 ]. Regarding the neuroprotective effect of naturally Lf in PD, the exogenous Lf has been widely recognized [ 30 , 89 , 100 , 101 , 102 , 103 , 104 ]. Moreover, studies have shown that Lf inhibits MPTP-induced excessive iron accumulation by upregulating the main iron regulatory proteins, divalent metal transporter (DMT1) and transferrin receptor (TFR), in cells [ 89 , 99 ].…”

“…A recent study showed that Lf may inhibit the Bcl-2/bax-mediated mitochondrial apoptosis pathway and the caspase protease family-mediated Fas/FasL exogenous apoptotic pathway [ 30 ]. Furthermore, Lf pretreatment partially reversed the decrease in mitochondrial potential, suggesting that Lf can protect cells from MPP + -induced oxidative stress by restoring mitochondrial function [ 30 , 104 ].…”

Human lactoferrin enhances the expression of transcription factor c-Fos in neuronal cultures under stimulated conditions

“…введение Лактоферрин (Лф) -полифункциональный белок из семейства трансферринов. Он активно исследуется в экспериментальных патологических моделях заболеваний человека в качестве антиаллергического, иммуномодулирующего, радиопротекторного агента [1,2], белка, способного ослабить прогрессирование нейродегенеративных заболеваний и стимулировать нейрорегенерацию [3]. Особый интерес вызывает способность Лф модулировать широкий спектр нейрональных процессов посредством изменения экспрессии генов, участвующих в долговременной нейропластичности (BDNF -Brain-Derived Neurotrophic Factor; CREB -cAMP Response Element-Binding protein, транскрипционный фактор; CAMK -Ca 2+ /calmodulin-dependent protein kinase, и др.)…”