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As terminally differentiated cells, neurons undergo aging with specific patterns.Understanding the characteristics of neural cell senescence and associated aging models is helpful to select appropriate models for the study of nervous system senescence.
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OBJECTIVE@#To study the protective effect of enhanced peroxisome proliferator activated receptor γ (PPARγ) pathway against apoptosis of long-term cultured primary nerve cells.@*METHODS@#A natural aging model was established in primary rat nerve cells by long-term culture for 22 days. The cells were divided into control group, 0.1, 1.0, 5.0, and 10 μmol/L GW9662 intervention groups, and 0.1, 1.0, 5.0, and 10 μmol/L pioglitazone intervention groups. The cell viability was assessed using MTT assay and the cell morphological changes were observed after the treatments to determine the optimal concentrations of GW9662 and pioglitazone. Double immunofluorescence labeling and flow cytometry were used to observe the changes in the number of viable cells and cell apoptosis following the treatments; immunocytochemical staining was used to assess the changes in the anti-oxidation ability of the treated cells.@*RESULTS@#The optimal concentrations of GW9662 and pioglitazone determined based on the cell viability and morphological changes were both 1 μmol/L. Compared with the control group, GW9662 treatment significantly lowered while pioglitazone significantly increased the total cell number and nerve cell counts ( < 0.05), and nerve cells in the cell cultures maintained a constant ratio at about 80% in all the groups ( > 0.05). GW9662 significantly enhanced while pioglitazone significantly lowered the cell apoptosis rates compared with the control group ( < 0.05). GW9662 obviously lowered SOD activity and GSH content in G group ( < 0.05) and increased MDA content in the cells ( < 0.05), and pioglitazone resulted in reverse changes in SOD, GSH and MDA contents in the cells ( < 0.05).@*CONCLUSIONS@#Activation of PPARγ pathway protects long-term cultured primary nerve cells by enhancing cellular anti-oxidant capacity and reducing cell apoptosis, suggesting a potential strategy for anti-aging treatment of the nervous system through intervention of the PPARγ pathway.
Subject(s)
Animals , Rats , Anilides , Pharmacology , Apoptosis , Cell Proliferation , Cell Survival , Cells, Cultured , Cellular Senescence , Physiology , Neurons , Cell Biology , PPAR gamma , Metabolism , Pioglitazone , PharmacologyABSTRACT
Objective To investigate the therapeutic effects of mesenchymal stem cells (MSCs) on N-methyl-N-nitrosourea (MNU)-induced retinal degeneration in C57BL mice.Methods Different doses of MNU (30 mg · kg-1,45 mg · kg-1,60 mg · kg-1,75 mg · kg-1 and 90 mg · kg-1) were injected to C57BL mice for 7 days.Then electroretinogram (ERG) detection and HE staining were performed to examine retinal electrophysiological function and morphological changes on day 1,day 3 and day 7 after MNU treatment,respectively.Then we could explore the optimum condition to establish stable animal model of retinitis pigmentosa.MSCs were transplanted to C57BL mice by intravitreal or tail intravenous injection.Then ERG detection and HE staining were performed to evaluate the effect of MSCs on retinitis pigmentosa induced by MNU.Results When compared with control group,30 mg · kg-1 and 45 mg · kg-1 MNU could cause mild retinal damage in morphology and function in mice;while 60 mg · kg-1 and above dose of MNU induced serious retinal damage,leading to decreased ERG amplitude of the retina (all P ＜ 0.001) and outer nuclear layer (ONL) thickness (all P ＜ 0.001).On day 1 and day 3 after single dose of 60 mg · kg-1 MNU injection,ERG amplitude of the retina was decreased,and outer nuclear layer thickness became thin;while the retinal damage was serious badly in morphological structure on day 7,with the ERG amplitude extinguished (all P ＜ 0.001),ONL thickness thin (all P ＜ 0.001) and internal and external nuclear layer fusion.When compared with MNU alone treatment group,following injection of 60 mg · kg-1 MNU for 1 day MSCs were transplanted to C57BL mice by intravitreal or tail intravenous injection,and the amplitude of ERG and retinal ONL thickness were increased on day 7 after MSCs transplantation (all P ＜ 0.001).Conclusion MSCs transplantation has a certain therapeutic effect on MNU-induced retinitis pigmentosa in C57BL mice.
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Objective To observe the effects of methionine enkephalin (M-Enk) on migration of macrophages from mice with impaired liver and its immunomodulatory mechanisms. MethodsLiver of mice was impaired by feeding CCl4 and macrophage migration inhibitory factor (MMIF) was produced by Con A-stimulated spleen lympho- cytes. Inhibition of macrophage migration was measured in reaction system by adding M-Enk. Results Migration of macrophages in both liver-impaired and control group were suppressed by MMIF, but the suppression might be re- versed by adding 1 μmol/L M-Enk (P＜0. 05). M-Enk could significantly inhibit in vitro both of the combination of MMIF with macrophages and production of MMIF from lymphocytes (P＜0. 01). Macrophages from liver-imparied group showed a higher sensitivity compared to the control group (P＜0. 05). ConclusionThe study suggests that opi- oid peptieds play an important role in the modulation of the immune response under stress as liver impairment.
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Objective To investigate the protective effect of 17?-estradiol (?E2) on cultured retinal neurons. Methods By using methods of the cultured retinal neurons, the effects of H 2O 2, ? E2, and tamoxifen, the estrogen receptor antagonist, on the cultured retinal neurons were observed. Results H 2O 2 significantly decreased cell viability in cultured retinal neurons in a dose- and time-dependent manner. When the retinal neurons were pretreated with ? E2 30 min prior to H 2O 2 treatment, cell viability was significantly increased (P