ABSTRACT
BACKGROUND@#Posttraumatic stress disorder (PTSD) and depression are highly comorbid. Psilocybin exerts substantial therapeutic effects on depression by promoting neuroplasticity. Fear extinction is a key process in the mechanism of first-line exposure-based therapies for PTSD. We hypothesized that psilocybin would facilitate fear extinction by promoting hippocampal neuroplasticity.@*METHODS@#First, we assessed the effects of psilocybin on percentage of freezing time in an auditory cued fear conditioning (FC) and fear extinction paradigm in mice. Psilocybin was administered 30 min before extinction training. Fear extinction testing was performed on the first day; fear extinction retrieval and fear renewal were tested on the sixth and seventh days, respectively. Furthermore, we verified the effect of psilocybin on hippocampal neuroplasticity using Golgi staining for the dendritic complexity and spine density, Western blotting for the protein levels of brain derived neurotrophic factor (BDNF) and mechanistic target of rapamycin (mTOR), and immunofluorescence staining for the numbers of doublecortin (DCX)- and bromodeoxyuridine (BrdU)-positive cells.@*RESULTS@#A single dose of psilocybin (2.5 mg/kg, i.p.) reduced the increase in the percentage of freezing time induced by FC at 24 h, 6th day and 7th day after administration. In terms of structural neuroplasticity, psilocybin rescued the decrease in hippocampal dendritic complexity and spine density induced by FC; in terms of neuroplasticity related proteins, psilocybin rescued the decrease in the protein levels of hippocampal BDNF and mTOR induced by FC; in terms of neurogenesis, psilocybin rescued the decrease in the numbers of DCX- and BrdU-positive cells in the hippocampal dentate gyrus induced by FC.@*CONCLUSIONS@#A single dose of psilocybin facilitated rapid and sustained fear extinction; this effect might be partially mediated by the promotion of hippocampal neuroplasticity. This study indicates that psilocybin may be a useful adjunct to exposure-based therapies for PTSD and other mental disorders characterized by failure of fear extinction.
Subject(s)
Humans , Mice , Animals , Psilocybin/metabolism , Fear , Extinction, Psychological , Brain-Derived Neurotrophic Factor/metabolism , Bromodeoxyuridine/pharmacology , Hippocampus/metabolism , Neuronal Plasticity , TOR Serine-Threonine Kinases/metabolismABSTRACT
Objective To observe the effect of hyperbaric oxygen (HBO)on neuropathic pain and detect the expression of Wnt/β-catenin signaling pathway in the mechanism of treatment. Methods A total of 30 healthy male SD rats were randomly divided into three groups (n =10):group S(sham group),group CCI(chronic sciatic nerve constrictive injury group),group HBO(HBO treat-ment for seven days group).Rats of group HBO received HBO one time per day for 7 days since the 1st day after surgery.Rats of group S and group CCI were just placed inside the chamber for approxi-mately 100 min,no HBO treatment.The mechanical withdrawal threshold (MWT)and thermal with-drawal latency (TWL)of all rats were measured on 1 d before CCI,1 d,3 d,5 d,7 d after CCI respec-tively.The animals were sacrificed after the last measurement of pain threshold,and the lumbar spinal cord specimen were taken to detect the expression of Wnt3a,β-catenin by immuno-histochemis-try and Western blot analysis.Results Compared with group S,MWT decreased significantly and TWL shortened significantly in CCT and HBO groups at 1,3,5,7 d after operation (P <0.05).Com-pared with group CCI,MWT was elevated and TWL was prolonged in group HBO at 1,3,5,7 d after operation (P <0.05).The Wnt3a,β-catenin expression increased after CCI treatment compared with group S and group HBO (P <0.05).Compared with group CCI,the expression of Wnt3a,β-catenin decreased significantly in the group HBO and group S at 7 d after operation (P <0.05).There was no significant difference between group S and group HBO.Conclusion HBO post-conditioning may relieve the neuropathic pain of rats by inhibiting the activation of spinal path of Wnt3a,β-catenin.
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Objective To observe the effect of ligustrazine (TMP) on the expression of connective tissue growth factor (CTGF) and osteopontin (OPN) in the renal tubulointerstitium of diabetic nephropathy (DN) rats. Methods Wistar rats were used to establish the models through intraperitoneal injection of onedose streptozotocin (STZ) and nephrectomy. Rats were divided into 5 groups at random: model group, blank control group, Lotensin (1.7 mg? kg- 1? d- 1) group, of high-and lowdosage of TMP groups (150, 50 mg? kg- 1? d- 1). Except the rats in blank group and model group, the rats received corresponding medicines according to the experimental design for 12 weeks.Volume of urine protein within 24 hours was examined in the 4th, the 8th and the 12 th week, OPN mRNA expression in the renal tubulointerstitium was detected by RT- PCR and CTGF was detected by means of immunohistochemistry. Results Compared with normal group, the volume of 24 h urine protein rised obviously (P
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Objective To assess the relationship between the concentration of total suspended particle (TSP) and cerebral-cardiovascular disease mortality of urban residents in Fushun city, China. Methods The data of cerebral-cardiovascular disease mortality and TSP concentration from 1999 to 2003 in Fushun city were collected. The association between TSP concentrations and the mortality of cerebral-cardiovascular diseases was analyzed using Poisson regression model adjusted for seasons, long-term patterns and meteorological variations using an ecological parametric method. Results As the concentration of TSP increased by 50 ?g/m3, OR of cerebral-cardiovascular disease mortality increase was 1.015 42 (95%CI=1.000 18-1.030 89) in the male group and 1.022 40 (95%CI=1.004 87-1.040 23) in the aged male group respectively, as 4-days lag TSP concentration increased by 50 ?g/m3, OR of cerebral-cardiovascular disease mortality increase was 1.008 26 (95%CI=1.000 57-1.016 02) in the whole people, 1.016 27 (95%CI=1.006 71-1.025 93) in the male group and 1.016 65 (95%CI=1.005 25-1.028 19) in the aged male group respectively. Conclusion Air pollution by TSP is considered as a risk factor for the increase of cerebral-cardiovascular disease mortality in Fushun city, China.