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

Abstract 

Uptake of ¹²³I-meta-iodobenzylguanidine (¹²³I-MIBG) is markedly reduced in the hearts of patients with Parkinson's disease. Although the mechanism of this reduction is unclear, ¹²⁵I-MIBG uptake is similarly reduced in the hearts of mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydroxypyridine (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 ¹²⁵I-MIBG was injected, the percent injected dose of ¹²⁵I-MIBG 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±0.67×10⁵ and 7.50±0.89×10⁵ pg/wet g) was significantly lower than that in control mice (9.21±0.97×10⁵ pg/wet g; P<.01 and P<.001, respectively). The NET density in mice receiving 10 or 40 mg/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 ¹²⁵I-MIBG and NET density decreased as the dose of MPTP increased. This study clearly shows that reduced cardiac ¹²⁵I-MIBG uptake in mice with MPTP-induced parkinsonism is closely related to the reduced NET density in postganglionic cardiac sympathetic nerve terminals.

Keywords: ¹²⁵I-meta-iodobenzylguanidine, Parkinson's disease, 1-Methyl-4-phenyl-1,2,3,6-tetrahydroxypyridine, Norepinephrine, Norepinephrine transporter