Neuroprotective Effect Of Orally Magnesium-l-threonate In MPTP Mice

Objective:Epidemiology research and clinical study indicated that magnesium deficiency is one of the pathogenetic factors of Parkinson's disease,animal experiments also demonstrated that magnesium deficiency can lead to Parkinson's disease.Our previous studies have confirmed MgSO₄ not improve magnesium concentration in cerebrospinal fluid,so this study was to investigate the role of oral Magnesium-L-threonate?MgT?which has high permeability capacityon the blood-brain barrier of MPTP model of Parkinson's disease.Methods:Eight-week-old male C57BL/6J mice weighing 18 to 22g were used and randomly divided into four groups after weighing:Control group,MPTP group?intraperitoneal injection,30 mg/kg/day for 7days?,MgSO₄-treated group?MPTP-treated+oral MgSO₄?and MgT-treated group?MPTP-treated+oral MgT,MgT set concentration gradient?.Through three aspects to evaluation the neuroprotective effect of oral Magnesium-L-threonate in MPTP mice:1.Behavioral measurement:Rotarod and Open field test were used to measure the spontaneous activity and anxiety condition effect of MgT to the mice,seven days after the last MPTP injection.2.Measurement of the number of the diapocynin?DA?neurons:TH immunohistochemistry was carried out to evaluation the effect of oral Magnesium-L-threonate to the loss of the DA neurons MPTP-induced in SNc.3.Evaluation of the neuroprotective mechanisms:At 1d after the last MPTP injection,animals were sacrificed,Glial Fibrillary Acidic Protein?GFAP?and Ionized calcium Binding adapter molecule1?IBa-1?immunohistochemistry were carried out to evaluation the neuroprotective effect of oral Magnesium-L-threonate to the loss of the DA neurons MPTP-induced in SNc.Results:1.Behavioral measurement.Rotarod:Compared with control group,the Rotarod time of MPTP model group was significantly shorter?40%,P<0.05?;Compared with model group,the Rotarod time of MgT group was significantly longer?35.6%,P<0.05?.Open field test:Compared with control group,the total distance and mean speed was significantly decreased37.6%and39.7%,respectively,P<0.01,Compared with model group,the total distance and mean speed of MgT group were significantly increased 38.5%and 50%,respectively,P<0.01.2.Measurement of the number of the diapocynin?DA?neurons:Compared with control group?27.6±7.9?,Positive neurons of Tyrosine hydorxylase?TH??10.4±5.6?in substantia nigra pars compacta was significantly reduced?P<0.01?,while MgT group?Mgconcentration is 1.2mM?increased the numbers of TH immunoreactive neurons?23.1±6.5?by 56.6%?P<0.01?.3.Evaluation of the neuroprotective mechanisms:Compared with control group,the GFAP and IBa-1 level in SN of MPTP model group were significantly increased 38.5%and 50%,respectively,P<0.01.Compared with MPTP model group,the GFAP and IBa-1 level in SN of MgT?Mgconcentration is 1.2mM?were significantly reduced?52.5%and 79.1%,respectively,P<0.01?.Conclusions:1.Oral administration of MgT significantly attenuated MPTP-induced the loss of DA in SNc,and improved motor function.2.MgT can significantly attenuated MPTP-induced the expression of GFAP and IBa-1,these results demonstrate that MgT exhibits profound neuroprotective effects in SN by attenuating neuroinflammatory responses and astroglial cell activation to attenuate DA neuron injury and improved motor function.