Cytosolic labile zinc accumulation in degenerating dopaminergic neurons of mouse brain after MPTP treatment.
High levels of labile zinc accumulate in degenerating neurons after brain injury, such as ischemic stroke, trauma, epilepsy, and hypoglycemia. Cytosolic zinc accumulation is also found in brain neurons undergoing apoptosis during development or after neuronal target ablation. Thus, staining with zinc-specific probes can be used to identify neuronal death in the brain. In this study, mice were intraperitoneally given four 20 mg/kg doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at 2-hour intervals, and dopaminergic neurons were then evaluated for zinc accumulation and apoptosis. In the substantia nigra pars compacta, zinc-specific fluorescent dyes revealed that all degenerating neurons, identified by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL), or acid fuchsin or Fluoro-Jade C staining, contained high levels of cytosolic labile zinc. Nuclear condensation/fragmentation was noted in dopaminergic neurons with cytosolic zinc accumulation, indicating apoptotic cell death. These findings support the supposition that cytosolic labile zinc accumulation is an indicator of degenerating dopaminergic neurons in animal models of Parkinson's disease.
Lee
Joo-Yong
JY
Asan Institute for Life Sciences, Asan Medical Center, Songpagu, Seoul 138-736, Republic of Korea. jlee@amc.seoul.kr
Son
Hyo Jin
HJ
Choi
Ji Hyun
JH
Cho
Eunsil
E
Kim
Jean
J
Chung
Sun Ju
SJ
Hwang
Onyou
O
Koh
Jae-Young
JY
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D020267:MPTP Poisoning / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D015032:Zinc / Q000378:metabolism*
D014446:Tyrosine 3-Monooxygenase; D015032:Zinc; D004298:Dopamine