Objective To investigate the effects and mechanisms of olfactory three-needle(OTN)electroacupuncture(EA)stimulation of the olfactory system on cognitive dysfunction,synaptic plasticity,and the gut microbiota in senesc...Objective To investigate the effects and mechanisms of olfactory three-needle(OTN)electroacupuncture(EA)stimulation of the olfactory system on cognitive dysfunction,synaptic plasticity,and the gut microbiota in senescence-accelerated mouse prone 8(SAMP8)mice.Methods Thirty-six SAMP8 mice were randomly divided into the SAMP8(P8),SAMP8+OTN(P8-OT),and SAMP8+nerve transection+OTN(P8-N-OT)groups according to a random number table(n=12 per group),and 12 accelerated senescence-resistant(SAMR1)mice were used as the control(R1)group.EA was performed at the Yintang(GV 29)and bilateral Yingxiang(LI 20)acupoints of SAMP8 mice for 4 weeks.The Morris water maze test,transmission electron microscopy,terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)staining,Nissl staining,Golgi staining,Western blot,and 16S rRNA sequencing were performed,respectively.Results Compared with the P8 group,OTN improved the cognitive behavior of SAMP8 mice,inhibited neuronal apoptosis,increased neuronal activity,and attenuated hippocampal synaptic dysfunction(P<0.05 or P<0.01).Moreover,the expression levels of synaptic plasticity-related proteins N-methyl-D-aspartate receptor 1(NMDAR1),NMDAR2B,synaptophysin(SYN),and postsynaptic density protein-95(PSD95)in hippocampus were increased by OTN treatment(P<0.05 or P<0.01).Furthermore,OTN greatly enhanced the brain-derived neurotrophic factor(BDNF)/cAMP-response element binding(CREB)signaling and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR)signaling compared with the P8 group(P<0.05 or P<0.01).However,the neuroprotective effect of OTN was attenuated by olfactory nerve truncation.Compared with the P8 group,OTN had a very limited effect on the fecal microbial structure and composition of SAMP8 mice,while specifically increased the genera Oscillospira and Sutterella(P<0.05).Interestingly,the P8-N-OT group showed an abnormal fecal microbiota with higher microbialα-diversity,Firmicutes/Bacteroidetes ratio and pathogenic bacteria(P<0.05 or展开更多
Objective: To investigate the molecular mechanisms underlying the beneficial effect of electroacupuncture(EA) in experimental models of Alzheimer’s disease(AD) in vivo. Methods: Senescenceaccelerated mouse prone 8(SA...Objective: To investigate the molecular mechanisms underlying the beneficial effect of electroacupuncture(EA) in experimental models of Alzheimer’s disease(AD) in vivo. Methods: Senescenceaccelerated mouse prone 8(SAMP8) mice were used as AD models and received EA at Yingxiang(LI 20, bilateral) and Yintang(GV 29) points for 20 days. For certain experiments, SAMP8 mice were injected intravenously with human fibrin(2 mg). The Morris water maze test was used to assess cognitive and memory abilities. The changes of tight junctions of blood-brain barrier(BBB) in mice were observed by transmission electron microscope. The expressions of fibrin, amyloid-β(Aβ), and ionized calcium-binding adapter molecule 1(IBa-1) in mouse hippocampus(CA1/CA3) were detected by reverse transcription-quantitative polymerase chain reaction(qRT-PCR), Western blot or immunohistochemical staining. The expression of fibrin in mouse plasma was detected by enzyme-linked immunosorbent assay. The expressions of tight junction proteins zonula occludens-1 and claudin-5 in hippocampus were detected by qRT-PCR and immunofluorescence staining.Apoptosis of hippocampal neurons was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) staining. Results: Fibrin was time-dependently deposited in the hippocampus of SAMP8mice and this was inhibited by EA treatment(P<0.05 or P<0.01). Furthermore, EA treatment suppressed the accumulation of Aβ in the hippocampus of SAMP8 mice(P<0.01), which was reversed by fibrin injection(P<0.05 or P<0.01). EA improved SAMP8 mice cognitive impairment and BBB permeability(P<0.05 or P<0.01).Moreover, EA decreased reactive oxygen species levels and neuroinflammation in the hippocampus of SAMP8mice, which was reversed by fibrin injection(P<0.05 or P<0.01). Mechanistically, EA inhibited the promoting effect of fibrin on the high mobility group box protein 1(HMGB1)/toll-like receptor 4(TLR4) and receptor for advanced glycation end products(RAGE)/nicotinamide adenine dinucleotide phosphate(NADPH展开更多
基金Supported by the National Natural Science Foundation of China(No.82074552)the Shaanxi Science and Technology Department Project(No.2018JM7041)Shaanxi Province TCM"Double Chain Integration"Young and Middle-Aged Scientific Research Innovation Team Construction Project(No.2022-SLRH-LJ-012)。
文摘Objective To investigate the effects and mechanisms of olfactory three-needle(OTN)electroacupuncture(EA)stimulation of the olfactory system on cognitive dysfunction,synaptic plasticity,and the gut microbiota in senescence-accelerated mouse prone 8(SAMP8)mice.Methods Thirty-six SAMP8 mice were randomly divided into the SAMP8(P8),SAMP8+OTN(P8-OT),and SAMP8+nerve transection+OTN(P8-N-OT)groups according to a random number table(n=12 per group),and 12 accelerated senescence-resistant(SAMR1)mice were used as the control(R1)group.EA was performed at the Yintang(GV 29)and bilateral Yingxiang(LI 20)acupoints of SAMP8 mice for 4 weeks.The Morris water maze test,transmission electron microscopy,terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)staining,Nissl staining,Golgi staining,Western blot,and 16S rRNA sequencing were performed,respectively.Results Compared with the P8 group,OTN improved the cognitive behavior of SAMP8 mice,inhibited neuronal apoptosis,increased neuronal activity,and attenuated hippocampal synaptic dysfunction(P<0.05 or P<0.01).Moreover,the expression levels of synaptic plasticity-related proteins N-methyl-D-aspartate receptor 1(NMDAR1),NMDAR2B,synaptophysin(SYN),and postsynaptic density protein-95(PSD95)in hippocampus were increased by OTN treatment(P<0.05 or P<0.01).Furthermore,OTN greatly enhanced the brain-derived neurotrophic factor(BDNF)/cAMP-response element binding(CREB)signaling and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR)signaling compared with the P8 group(P<0.05 or P<0.01).However,the neuroprotective effect of OTN was attenuated by olfactory nerve truncation.Compared with the P8 group,OTN had a very limited effect on the fecal microbial structure and composition of SAMP8 mice,while specifically increased the genera Oscillospira and Sutterella(P<0.05).Interestingly,the P8-N-OT group showed an abnormal fecal microbiota with higher microbialα-diversity,Firmicutes/Bacteroidetes ratio and pathogenic bacteria(P<0.05 or
基金Supported by the National Natural Science Foundation of China (No.82074552)Shaanxi Science and Technology Department Project (No.2018JM7041)Shaanxi Province TCM "Double Chain Integration" Young and Middle-Aged Scientific Research Innovation Team Construction Project (No.2022-SLRH-LJ-012)。
文摘Objective: To investigate the molecular mechanisms underlying the beneficial effect of electroacupuncture(EA) in experimental models of Alzheimer’s disease(AD) in vivo. Methods: Senescenceaccelerated mouse prone 8(SAMP8) mice were used as AD models and received EA at Yingxiang(LI 20, bilateral) and Yintang(GV 29) points for 20 days. For certain experiments, SAMP8 mice were injected intravenously with human fibrin(2 mg). The Morris water maze test was used to assess cognitive and memory abilities. The changes of tight junctions of blood-brain barrier(BBB) in mice were observed by transmission electron microscope. The expressions of fibrin, amyloid-β(Aβ), and ionized calcium-binding adapter molecule 1(IBa-1) in mouse hippocampus(CA1/CA3) were detected by reverse transcription-quantitative polymerase chain reaction(qRT-PCR), Western blot or immunohistochemical staining. The expression of fibrin in mouse plasma was detected by enzyme-linked immunosorbent assay. The expressions of tight junction proteins zonula occludens-1 and claudin-5 in hippocampus were detected by qRT-PCR and immunofluorescence staining.Apoptosis of hippocampal neurons was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) staining. Results: Fibrin was time-dependently deposited in the hippocampus of SAMP8mice and this was inhibited by EA treatment(P<0.05 or P<0.01). Furthermore, EA treatment suppressed the accumulation of Aβ in the hippocampus of SAMP8 mice(P<0.01), which was reversed by fibrin injection(P<0.05 or P<0.01). EA improved SAMP8 mice cognitive impairment and BBB permeability(P<0.05 or P<0.01).Moreover, EA decreased reactive oxygen species levels and neuroinflammation in the hippocampus of SAMP8mice, which was reversed by fibrin injection(P<0.05 or P<0.01). Mechanistically, EA inhibited the promoting effect of fibrin on the high mobility group box protein 1(HMGB1)/toll-like receptor 4(TLR4) and receptor for advanced glycation end products(RAGE)/nicotinamide adenine dinucleotide phosphate(NADPH
