The biologically active substance P (SP) N-terminal metabolite SP1–7 has been reported to modulate several neural processes such as learning, locomotor activity and reaction to opioid withdrawal. Although all these processes are believed to be associated with dopaminergic transmission no evidence of an interaction between SP1–7 and dopamine in the case of morphine withdrawal has so far been reported. Therefore, in this work we applied in vivo microdialysis to investigate the effect of SP1–7 injection into the ventral tegmental area on dopamine release in nucleus accumbens of male rats during naloxone precipitated morphine withdrawal. The result showed that the heptapeptide enhances dopamine release and also elevates the level of the dopamine metabolite dihydroxyphenylacetic acid in this brain area. It was suggested that the observed action of the SP fragment on the dopamine system represents the underlying mechanism for a previously observed ability of SP1–7 to counteract the aversion response to morphine withdrawal. 相似文献
Background: Despite years of research, the treatment of acute kidney injury (AKI) remains a significant challenge. Animal studies presented causal links between elevated regulatory T cell (Treg) response and better prognosis in AKI. Previous studies in mice and humans showed that TIM-3+ Treg cells were more potent than TIM-3- Treg cells. In this study, we investigated the role of TIM-3 in Treg in AKI patients.
Methods: Peripheral blood from AKI patients and healthy controls were gathered, and TIM-3+ Treg subset was examined.
Results: Compared to healthy controls, the AKI patients presented a significant upregulation in the frequency of circulating CD4+CD25+ T cells; however, the majority of this increase was from the CD4+CD25+TIM-3- subset, and the frequency of CD4+CD25+TIM-3+ T cells was downregulated in AKI patients. In both healthy controls and AKI patients, the CD4+CD25+TIM-3+ T cells expressed higher levels of Foxp3, and were more potent at expressing LFA-1, LAG-3, CTLA-4, IL-10 and TGF-β. In addition, the CD4+CD25+TIM-3+ T cells from both healthy controls and AKI patients presented higher capacity to suppress CD4+CD25- T cell proliferation than the CD4+CD25+TIM-3- T cells. Interestingly, the total CD4+CD25+ T cells from AKI patients presented significantly lower inhibitory capacity than those from healthy controls, indicating that the low frequency of CD4+CD25+TIM-3+ T cells was restricting the efficacy of the Treg responses in AKI patients.
Conclusions: We demonstrated that TIM-3 downregulation impaired the function of Treg cells in AKI. The therapeutic potential of CD4+CD25+TIM-3+ T cells in AKI should be investigated in future studies. 相似文献
Huntington's disease is a progressive, inherited neurodegenerative disorder characterized by the loss of subsets of neurons primarily in the striatum. In this study, we assessed the neuroprotective effect of lithium against striatal lesion formation in a rat model of Huntington's disease in which quinolinic acid was unilaterally infused into the striatum. For this purpose, we used a dopamine receptor autoradiography and glutamic acid decarboxylase mRNA in situ hybridization analysis, methods previously shown to be adequate for quantitative analysis of the excitotoxin-induced striatal lesion size.Here we demonstrated that subcutaneous injections of LiCl for 16 days prior to quinolinic acid infusion considerably reduced the size of quinolinic acid-induced striatal lesion. Furthermore, these lithium pre-treatments also decreased the number of striatal neurons labeled with the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. Immunohistochemistry and western blotting demonstrated that lithium-elicited neuroprotection was associated with an increase in Bcl-2 protein levels.Our results raise the possibility that lithium may be considered as a neuroprotective agent in treatment of neurodegenerative diseases such as Huntington's disease. 相似文献
Transfer of encephalitogenic, CD4+ T lymphocyte lines into syngeneic adult Lewis rats not only leads to the development of experimental autoimmune encephalomyelitis (EAE), but, in addition, to the expansion of counterregulatory, CD8+ T lymphocyte clones which are able to lyse specifically the encephalitogenic T cells in vitro and to neutralize their encephalitogenic capacity in vivo. In striking contrast, in neonatal rats, which still lack myelin (autoantigens), injection of the same encephalitogenic lines neither mediates EAE, nor confers protection in later life against the myelin-specific T cells. In fact, this treatment results in the life-long functional elimination of counterregulatory, clonotypic CD8+ T lymphocytes, which cannot even be reinduced by repeated injections of the relevant CD4+ T line. These data seem to point to a self-protective T cell control mechanism which is developed within the immune system prior to, and thus independent of the appearance of the appropriate self antigen. 相似文献
A pair of rat anti-mouse CD4 monoclonal antibodies (mAb) have been selected which bind to different epitopes of the molecule. Both the mAb are rat IgG2b and show clear synergistic activity in complement lysis in vitro. When injected together in vivo, they exhibit an improved immunosuppressive effect, compared to each antibody alone, on allogeneic graft rejection, humoral responses and on tolerance induction. Limiting dilution analysis indicates that the in vivo depletion of interleukin 2-producing cells is improved using both mAb by 2-3-fold over that obtained with the individual antibodies. As little as 60 ng per mouse of the CD4 antibody pair was sufficient to allow the induction of tolerance to human gamma-globulin, even without elimination of the CD4+ cells. The results suggest that appropriate antibody pairs may be good candidates for effective immunosuppressive serotherapy in man. 相似文献