Quantitative imaging of Cu,Fe,Mn and Zn in the L-DOPA-treated unilateral 6-hydroxydopamine Parkinson's disease mouse model by LA-ICP-MS

Abstract

Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) imaging was used to generate quantitative elemental images of brain sections of mice with unilateral 6-hydroxydopamine (6-OHDA) lesions. In previous studies, an external calibration and regional image analysis strategy was developed and applied to serial sections at the level of the midbrain (including the substantia nigra, SN) of one 6-OHDA mouse. In this work, this strategy was validated by measuring sections at the striatum level in 18 6-OHDA-lesioned mice. 12 of these animals were treated with 6 mg kg⁻¹ L-DOPA (L-3,4-dihydroxyphenylalanine, LD). The first estimate of the variance of in situ metal concentrations between animals amounting to 24% for Fe, 18% for Cu, 19% for Zn and 13% for Mn (RSD) in the cortex are provided. Concentrations of Fe, Cu, Mn and Zn were approximately identical in LD treated animals and controls. However, significantly lower concentrations of Fe (−7%) in the ventral and of Cu (−7%) in the dorsal striatum of the lesioned compared to the healthy hemisphere of all animals were detected. In controls, but not in LD treated animals, higher Cu concentrations were detected in the periventricular zone. The ratios of ventricular to parenchymal Cu can be considered as a measure of Cu efflux. The side difference of these values was significantly reduced by LD. Similar responses to LD countervailing at the healthy and 6-OHDA-lesioned sides have been described for other parameters such as dopamine receptors and transporters.