ABSTRACT
Objective:To explore the improvement and its mechanism of minocycline on sevoflurane anesthesia induced cognitive dysfunction in aged mice.Methods:Totally 75 aged clean-grade C57BL/6 mice were randomly divided into control (Con) group( n=25), sevoflurane (Sev) group( n=25) and sevoflurane + minocycline (Sev+ Min) group( n=25). Anesthetic injury was induced by 3% sevoflurane (2 h/d for 3 days) in Sev group. Minocycline (50 mg/kg) was injected intraperitoneally first, and then 3% sevoflurane (2 h/d for 3 days) anesthesia was performed in Sev+ Min group. Saline alone was injected intraperitoneally (once a day for 3 days) in Con group.The spatial memory function was detected by Morris water maze experiments. BrdU was used to label new neuron and the proliferation was observed by immunohistochemistry. The field excitatory postsynaptic potential (fEPSP) slope was measured in hippocampal dentate gyrus (DG) region of isolated brain slices by electricphysiological technique.The data were analyzed by repeated measures analysis of variance and SNK-q test using SPSS 21.0 software. Results:Results from positioning navigation experiment showed that the group×time interaction effect of mice was significant( F=15.65, P<0.01). On the 6th day after anesthesia, compared with Con group, the escape latency of the original platform in Sev group was significantly increased ( q=4.35, P<0.05) in space exploration experiment, while the target quadrant time ratio ( q=6.15, P<0.05))and the mean annulus crossings ( q=6.45, P<0.05) were significantly decreased. Compared with Sev group, the escape latency in Sev+ Min group was significantly decreased ( q=3.01, P<0.05), while the target quadrant time ratio ( q=3.21, P<0.05) and the mean annulus crossings ( q=3.48, P<0.05) were significantly increased. In immunohistochemistry experiment, the number of BrdU positive cells in Sev group was significantly reduced ((227.45±43.25), q=8.67, P<0.01) compared with Con group (355.87±62.58). Compared with Sev group, the number of BrdU positive cells in Sev+ Min group was significantly increased ((338.73±47.27), q=8.68, P<0.01). In electricphysiological test, the fEPSP slope after high frequency stimulation in Sev group ((126.83±25.67)%, q=6.18, P<0.01)) was significantly lower than that in Con group((214.38±43.42)%). In Sev+ Min group, the fEPSP slope was significantly higher ((178.49±32.67)%, q=3.64, P<0.05) than that in Sev group. Conclusion:Sevoflurane anesthesia can induce the short-term cognitive dysfunction in aged mice, and its mechanism is related to inhibiting neuron proliferation and synaptic plasticity. Minocycline can alleviate the damage caused by sevoflurane.
ABSTRACT
Objective To study the function of LSD1 in the development of neurons and the influence of LSD1 on mood and memory-related behavior in mice. Methods The LSD1(flox / flox) transgenic mice were crossed with Nestin?cre(Tg) transgenic mice, using Cre?LoxP recombination system, to generate LSD1 conditional knockout of neural stem cell ( LSD1?CKO) mice, LSD1(flox/ flox) Nestin?cre(Tg) mice, and LSD1(flox/ flox) mice as control. The neuron proliferation in LSD1?CKO mice was further detected by immunofluorescence staining. At the same time, the mood and memory?related behavior of LSD1?CKO mice were examined using several methods:sucrose preference test ( SPT) , forced swimming test ( FST) and novel?object recognition ( NOR) assay. Results In the LSD1 brain?specific CKO mice, the neuron proliferation rate in the hippocampus was significantly reduced ( P=0. 023 ) , the preference for sucrose was reduced ( P =0. 0075 ) , immobility duration during the forced swimming test was increased (P<0. 05), and LSD1?CKO mice also exhibits memory?decline (P=0. 0019) during the novel?object recognition test. Conclusions Depletion of LSD1 in mouse brain neural stem cells leads to significant reduction of the neuron proliferation in the hippocampus. LSD1?CKO mice show more negative emotions and memory impairment.