Reduced I-125-meta-iodobenzylguanidine uptake and norepinephrine transporter density in the hearts of mice with MPTP-induced parkinsonism

Uptake of I-123-meta-iodobenzylguanidine (I-123-MIBG) is markedly reduced in the hearts of patients with Parkinson's disease. Although the mechanism of this reduction is unclear, I-125-MIBG uptake is similarly reduced in the hearts of mice with 1-methyl-4-plienyl-1,2,3, 6-tetraliydroxypyridine (MPTP)-induced parkinsonism. Three groups of ten 15-week-old C57BL6 mice received intraperitoneal injections of (1) saline (control), (2) 10 mg/kg MPTP or (3) 40 mg/kg MPTP. After 0.185 MBq of I-125-MTBG was injected, the percent injected dose of I-125-MTBG per gram of tissue (%ID/g) was determined and cardiac concentrations of norepinephrine were measured. Cardiac concentrations of norepinephrine transporter (NET) were measured in three groups of twenty 15-week-old C57BL6 mice receiving these same treatments. The %ID/g in mice receiving 10 or 40 mg/kg MPTP (5.7 +/- 1.1 and 4.4 +/- 1.2%/g) was significantly lower than that in control mice (11.3 +/- 2.2%/g- P <.00001 and P <.0000001, respectively). The norepinephrine concentration in mice receiving 10 or 40 mg/kg MPTP (7.86 +/- 0.67 x 10(5) and 7.50 +/- 0.89 x 10(5) pg/wet g) was significantly lower than that in control mice (9.21 +/- 0.97 x 10(5) pg/Nvet g; P <.01 and P <.001. respectively). The NET density in mice receiving 10 or 40 ing/kg MPTP (81 +/- 12, 61 +/- 7 fmol/mg protein) was significantly lower than that in control mice (126 +/- 7 fmol/mg protein; P <.000001 and P <.0000001, respectively). The %ID/g of 125 I-MIBG and NET density decreased as the dose of MPTP increased. This study clearly shows that reduced cardiac I-125-MIBG uptake in mice with MPTP-induced parkinsonism is closely related to the reduced NET density in postganglionic cardiac sympathetic nerve terminals. (c) 2006 Elsevier Inc. All rights reserved.