title: Repeated intra-nigrostriatal injection of phorbol myristate acetate induces microglial senescence in adult rats.
abstract: Phorbol myristate acetate (PMA), as a potent tumor promoter, may induce microglial senescence. The present study investigated the effect of PMA infection on microglial senescence. From 58 male Sprague‑Dawley rats, 10 were randomly selected and divided into a PMA injection group, containing five rats (0.5 µg/µl PMA) and a control group, containing five rats (commensurable 0.9% saline). Immunofluorescent staining of Iba‑1 and enzyme‑linked immunosorbent assay analyses of the expression levels of tumor necrosis factor (TNF)‑α and interleukin (IL)‑1 β were performed in these two groups. The remaining 48 rats were randomly divided into the following three groups, each containing 16 rats: Repeated injection control group (commensurable normal saline, once a week for 4 weeks), single PMA injection group (0.5 µg/µl PMA, once in the first week) and repeated injection PMA group (0.5 µg/µl PMA, once a week for 4 weeks). The expression levels of p21, detected using double immunofluorescence staining with Iba‑1, and β‑galactosidase, via double immunohistochemical staining of Iba‑1, were examined in these three groups. The results indicated that a single injection of PMA did not change the microglial morphology and had no significant effects on the expression levels of TNF‑α and IL‑1β, compared with the control group (P>0.05). Following four repeated injections of PMA, the microglia in the substantia nigra presented with features of senescence, characterized by increased expression levels of β-galactosidase (P<0.001) and p21 (P<0.001), compared with the repeated injection control group. In conclusion, repeated intra-nigrostriatal treatment with PMA induced microglial senescence with increased expression levels of β-galactosidase and p21 in the substantia nigra of the rats.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Xiao-Guang
authors.initials: XG
authors.lastname: Luo
authors.affiliation: Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Yu
authors.affiliation: Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Department of Nuclear Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Ya-Fu
authors.initials: YF
authors.lastname: Yin
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Shang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Zhi-Yi
authors.initials: ZY
authors.lastname: He
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D016922:Cellular Senescence / Q000187:drug effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D007276:Injections, Intraventricular; D008297:Male; D017628:Microglia / Q000502:physiology*; D010300:Parkinson Disease / Q000473:pathology; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects* / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D002273:Carcinogens; D050759:Cyclin-Dependent Kinase Inhibitor p21; D013755:Tetradecanoylphorbol Acetate