动物模型与人类重大疾病机理重点实验室知识库

Phosphorylation of a-synuclein at serine 129 (P-Ser 129 a-syn) is involved in the pathogenesis ofParkinson’s disease (PD) and Lewy body (LB) formation. However, there is no clear evidence indicates the quan-titative relation of P-Ser 129 a-syn accumulation and dopaminergic cell loss, LBs pathology and the affected brainareas in PD monkeys. Here, pathological changes in the substantia nigra (SN) and PD-related brain areas weremeasured in aged monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) utilizing amodeling-recovery-remodeling strategy. Compared to age-matched controls, the MPTP-treated monkeys showedsignificantly reduced tyrosine hydroxylase (TH)-positive neurons and increased P-Ser 129 a-syn-positive aggre-gations in the SN. Double-labeling Immunofluorescence found some TH-positive neurons to be co-localized withP-Ser129 a-syn in the SN, suggesting the inverse correlation between P-Ser 129 a-syn aggregations and dopamin-ergic cell loss in the SN may represent an interactive association related to the progression of the PD symptomsin the model. P-Ser 129 a-syn aggregations or LB-like pathology was also found in the midbrain and the neocor-tex, specifically in the oculomotor nucleus (CN III), temporal cortex (TC), prefrontal cortex (PFC) and in cellssurrounding the third ventricle. Notably, the occipital cortex (OC) was P-Ser 129 a-syn negative. The findingsof LB-like pathologies, dopaminergic cell loss and the stability of the PD symptoms in this model suggest thatthe modeling-recovery-remodeling strategy in aged monkeys may provide a new platform for biomedical investi-gations into the pathogenesis of PD and potential therapeutic development. ? 2018 IBRO. Published by Elsevier Ltd.All rights reserved.