1H MRS identifies lactate rise in the striatum of MPTP‐treated C57BL/6 mice

Abstract

Mitochondrial dysfunction has been implicated in the death of nigrostriatal dopaminergic neurons in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated experimental models of Parkinson's disease (PD). Here we utilized proton magnetic resonance spectroscopy (1H MRS) to identify changes in energy metabolism in the striatum of MPTP‐treated C57BL/6 mice. Remarkable increases in lactate/creatine (Lac/Cr) ratio were observed at 2 h and then quickly returned to about the basal level by 7 h after injection of MPTP. Neurochemical and Western blot analyses revealed that dopamine contents and protein levels of tyrosine hydroxylase and dopamine transporter in the striatum were profoundly decreased at 3 days after MPTP treatment. Pretreatment with deprenyl, a monoamine oxidase B inhibitor, or GBR‐12909, a dopamine uptake inhibitor, almost completely attenuated both the increases in striatal Lac/Cr ratio and the subsequent loss of dopaminergic nerve terminals in MPTP‐treated mice. The present study indicates that 1H MRS is a sensitive measure of biochemical alterations of the brain in a mouse model of PD, and further shows that the increases in striatal Lac/Cr ratio induced by MPTP may be associated with mitochondrial energy crisis, followed by dopaminergic neurotoxicity.

Part of CIRS Nexus · Curated by Lauren Lowenstein, The Biotoxin Lady

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