Treatment Of Magnesium-L-Threonate Elevates The Magnesium Level In The Cerebrospinal Fluid And Attenuates Motor Deficits And Dopamine Neuron Loss In A Mouse Model Of Parkinson’s disease

Abstract

Yanling Shen,1,2,* Ling Dai,1,* Haibo Tian,1,3 Runnan Xu,1 Fuying Li,4 Zhuohang Li,1 Jeremy Zhou,5 Liping Wang,5 Jianghui Dong,1,5 Liyuan Sun1,4 1Department of Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical University, Guilin 541004, Guangxi, People’s Republic of China; 2Department of Pathology, Affiliated Chenggong Hospital, Xiamen University, Xiamen, Fujian 361000, People’s Republic of China; 3Department of Pathology, Fuling Central Hospital of Chongqing City, Chongqing 408099, People’s Republic of China; 4Department of Neurology and Neurological Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan; 5School of Pharmacy and Medical Sciences, and UniSA Cancer Research Institute, University of South Australia, Adelaide, SA 5001, Australia*These authors contributed equally to this workCorrespondence: Jianghui DongDepartment of Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical University, Guilin 541004, Guangxi, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected] SunDepartment of Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical University, Guilin 541004, Guangxi, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected]: Epidemiology research has demonstrated that magnesium (Mg) deficiency is associated with a high incidence of Parkinson’s disease (PD). It is known that the systemic administration of MgSO4 is not able to elevate the Mg concentration in cerebrospinal fluid (CSF). This study aims to verify the protective effect of magnesium-L-threonate (MgT) in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) mouse model.Methods: C57BL/6J mice were orally administered MgT or MgSO4 for 4 weeks, and received MPTP in the third week. After analysis of open-field and rotarod tests on the last day, tyrosine hydroxylase (TH) immunopositive cells and protein levels were quantified in the substantia nigra pars compacta (SNpc) and striatum. The expression of inducible nitric oxide synthase (iNOS) level was evaluated. Mg concentration in serum and CSF was measured after oral administration of MgSO4 or MgT in normal mice. Mg concentration in the CSF was increased in the mice treated with MgT but not MgSO4.Results: The total distance and mean speed in open-field tests, and the time spent on rotarod in the MgT group were increased, compared with MPTP group. The MgT treatment but not MgSO4 dose-dependently attenuated the loss of TH-positive neurons, and the reduction of the TH expression in the SNpc. The MgT treatment also inhibited the expression of iNOS as measured by immunohistochemistry and Western blots. Double-immunofluorescence staining of TH and iNOS showed iNOS-positive cells were collocalized for TH-positive cells.Conclusion: The treatment with MgT is associated with an increase of Mg in the CSF. MgT, rather than MgSO4, can significantly attenuate MPTP-induced motor deficits and dopamine (DA) neuron loss.Keywords: Parkinson’s disease, magnesium-L-threonate, cerebrospinal fluid, magnesium

Keywords

• parkinson’s disease
• magnesium-l-threonate
• cerebrospinal fluid
• magnesium