ABSTRACT
Objective:To explore how an enriched environment promotes synaptic remodeling in the hippocampus after cerebral ischemia.Methods:Among 60 clean, adult, male C57BL/6 mice, 16 were randomly selected into a sham operation group, while the remaining 44 underwent permanent left middle cerebral artery embolization. The 32 mice with successful modeling were randomly divided into a normal environment group and an enriched environment group, each of 16. The enriched environment group lived in an enriched environment for 28 days, while the other two groups were raised in normal conditions. The number of synapses in the CA3 area of the hippocampus was then measured using transmission electron microscopy, and the expression of Wnt7a, Dvl1, β-catenin, synaptophysin (SYN) and PSD-95 in the hippocampus were measured using western blotting.Results:Compared with the normal environment group, the average protein expression levels of Wnt7a, Dvl1, β-catenin, SYN and PSD-95 were all significantly higher in the enriched environment group. The number of synapses in the CA3 region of the enriched environment group was also significantly higher than in the normal environment group.Conclusion:An enriched environment can activate the Wnt7a-β-catenin-Dvl1 signaling pathway in the hippocampus after cerebral ischemia to promote synaptic remodeling, at least in mice.
ABSTRACT
Objective:To study the effect of Ganoderma triterpenoids combined with exogenous monosialoteterahexosyl ganglioside (GM1) on cognitive dysfunction in rats with epilepsy. Methods:A total of 75 Sprague-Dawley rats were divided randomly into blank control group, epileptic model group, Ganoderma triterpenoids group, GM1 group and GM1 combined with Ganoderma triterpenoids group (combination group), with 15 rats in each group. All the groups, except the blank control group, were intraperitoneally injected with pentylenetetrazol (PTZ) 35 mg/kg once a day for 28 days. Medication groups were given corresponding administration based on daily intraperitoneal injection of PTZ. They were tested with Morris Water Maze; and were observed with transmission electron microscopy and HE staining for hippocampal neurons. Real-time quantitative polymerase chain reaction was used to detect the expression of actin-binding protein (Cofilin), synaptophysin (SYN) and growth-associated protein 43 (GAP-43) mRNA in hippocampus of rats. Results:Compared with the blank control group, the escape lantency prolonged in the epileptic model group in all the time points (P < 0.05). Compared with the epileptic model group, the escape lantency shortened in the treatment groups somewhen (P < 0.05). Compared with the epileptic model group, the number of crossing the platform increased in the treatment groups (P < 0.01), and the time of staying in the target quadrant prolonged (P < 0.01); while the number of pyramidal cells increased, the nuclear lysis and fragmentation reduced, the structure of neurons and the number of synapses improved， as well as the organelle structure. Compared with the blank control group, the expression of Cofilin mRNA increased (P < 0.05), and the expression of SYN mRNA and GAP-43 mRNA decreased (P < 0.05) in the epileptic model group; compared with the epileptic model group, the expression of Cofilin mRNA decreased (P < 0.05), and the expression of SYN mRNA increased (P < 0.05) in all the treatment groups, while the expression of GAP-43 mRNA increased (P < 0.05) only in the combination group. Conclusion:Ganoderma triterpenoids, GM1 and their combination can improve the learning and memory abilities of epileptic rats, which may be associated with increasing the expression of SYN and GAP-43, decreasing the expression of Cofilin, to promote the synaptic remodeling of hippocampal tissue and protect brain neurons from PTZ-induced epilepsy.
ABSTRACT
Objective To investigate the role of nuclear transcription factor kappa B (NF-κB) -matrix metalloproteinase-9 (MMP-9) signaling pathway in delayed encephalopathy after acute carbon monoxide poisoning (DEACMP). Methods 150 male SD rats were randomly assigned to air control group (AC group) , CO poisoning group (CO group) , pyrrolidine thiocarbamate (PDTC) + CO poisoning group (PC group). DEACMP model was reconstructed by modified intraperitoneal injections. The 1, 3, 7, 14, and 21 d after intraperitoneal injection were observed here by different approaches. Morris water maze test was used to test the learning and memory ability of rats.HE staining was used to observe the morphology of hippocampal CA3 cells. Immunofluorescence and Western Blot methods were used to detect the expression of NF-κB and MMP-9. RT-PCR was used to measure the expression of MMP-9 mRN A. Transmission electron microscopy was used to observe the ultrastructure of synapses. Results After14 days, the average intubation period of CO group was longer than that of AC group (P < 0.05) , and that of PC group was shorter than that of CO group (P < 0.05). However, average intubation period of PC group was longer than that of AC group (P< 0.05). In CO group, the expression of NF-κB in hippocampus increased (day 1). At day 3, the expression of NF-κB rapidly increased. The expression of MMP-9 gene and protein increased in the first three days and then decreased thereafter. The expression of NF-κB and MMP-9 in PC group was lower than that in CO group (P < 0.05) , while it was higher than AC group (P < 0.05). The peak value of apoptosis in CO group was delayed to 7-14 d after exposure, the apoptotic cells in PC group decreased significantly, and it was obvious on the 14 th day.Electron microscopy showed that the damage of synapses ultrastructure in CO group was significantly heavier than that in PC group on the 14 th day. Conclusions NF-κB-MMP-9 signal pathway leads to DEACMP, and PDTC could alleviate the impairment of learning and memory ability in rats with acute CO poisoning.