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

Purpose

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

Acknowledgments

This work was supported by the National Natural Science Foundation of China (81260205) and Guangxi Natural Science Foundation (2018GXNSFAA281246).

Disclosure

The authors report no conflicts of interest in this work.