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61.
Golo Kronenberg Imke Kirste Dragos Inta Sabine Chourbaji Isabella Heuser Matthias Endres Peter Gass 《European archives of psychiatry and clinical neuroscience》2009,259(8):499-504
Glucocorticoid receptor (GR) heterozygous mice (GR+/−
) represent a valuable animal model for major depression. GR+/−
mice show a depression-related phenotype characterized by increased learned helplessness on the behavioral level and neuroendocrine
alterations with hypothalamo-pituitary-adrenal (HPA) axis overdrive characteristic of depression. Hippocampal brain-derived
neurotrophic factor (BDNF) levels have also been shown to be reduced in GR+/−
animals. Because adult hippocampal neurogenesis has been implicated in the pathophysiology of affective disorders, we studied
here the effects of the GR+/−
genotype on neurogenesis in vivo. In a 2 × 2 design, GR+/−
mice and GR+/+ littermate controls were either subjected to 1 h of restraint stress or left undisturbed in their home cages after intraperitoneal
injection of BrdU. Stress exposure and BrdU injections were performed once daily for 7 days and neurogenesis analyzed 4 weeks
later. BrdU cell counts were significantly reduced as an effect of GR+/−
genotype and as an effect of stress. Majority of the BrdU+ cells showed co-labeling with mature neuronal marker NeuN or astrocytic
marker S100β with no further significant effect of either experimental condition or of genotype. In sum, this results in reduced
neurogenesis in GR+/−
mice which is further repressed by restraint stress. Our results, thus, reinforce the link between reduced neurogenesis,
stress, neurotrophins, and behavioral symptoms of and susceptibility to depression. 相似文献
62.
Inhibition of histone deacetylation protects wildtype but not gelsolin-deficient mice from ischemic brain injury 总被引:1,自引:0,他引:1
Yildirim F Gertz K Kronenberg G Harms C Fink KB Meisel A Endres M 《Experimental neurology》2008,210(2):531-542
Acetylation/deactylation of histones is an important mechanism to regulate gene expression and chromatin remodeling. We have previously demonstrated that the HDAC inhibitor trichostatin A (TSA) protects cortical neurons from oxygen/glucose deprivation in vitro which is mediated--at least in part--via the up regulation of gelsolin expression. Here, we demonstrate that TSA treatment dose-dependently enhances histone acetylation in brains of wildtype mice as evidenced by immunoblots of total brain lysates and immunocytochemical staining. Along with increased histone acetylation dose-dependent up regulation of gelsolin protein was observed. Levels of filamentous actin were largely decreased by TSA pre-treatment in brain of wildtype but not gelsolin-deficient mice. When exposed to 1 h filamentous occlusion of the middle cerebral artery followed by reperfusion TSA pre-treated wildtype mice developed significantly smaller cerebral lesion volumes and tended to have improved neurological deficit scores compared to vehicle-treated mice. These protective effects could not be explained by apparent changes in physiological parameters. In contrast to wildtype mice, TSA pre-treatment did not protect gelsolin-deficient mice against MCAo/reperfusion suggesting that enhanced gelsolin expression is an important mechanism by which TSA protects against ischemic brain injury. Our results suggest that HDAC inhibitors such as TSA are a promising therapeutic strategy for reducing brain injury following cerebral ischemia. 相似文献
63.
64.
65.
Petzold C Rubert M Lyngstadaas SP Ellingsen JE Monjo M 《Journal of biomedical materials research. Part A》2011,96(1):83-92
The aim of this study was to design implant surfaces that attach less to bone but at the same time improve osseous healing for use as temporary bone fracture plates. The strategy was to combine the nonadhesive properties of smooth titanium (Ti) surfaces with the differentiative and anti-inflammatory properties of eicosapentaenoic acid (EPA). Machined Ti implant surfaces coated with a layer of EPA, with or without UV irradiation, were characterized by X-ray photoelectron spectroscopy, and their in vivo performance was evaluated in New Zealand White rabbits. The performance of the functionalised implants was analyzed after 10 weeks of healing by mechanical pull-out testing, molecular biology, and histological and microcomputed tomography analysis. The results indicate that surface functionalization with UV light can reduce bone attachment and volumetric bone mineral density in the peri-implant bone tissue. The presence of EPA on the surfaces enhanced this effect further. Gene expression of bone formation markers showed a trend toward higher mRNA levels in all EPA treated groups. The histological analyses demonstrated lower inflammation in the UV-irradiated group and immature bone formation in all the groups. In conclusion, surface functionalization of Ti implants with UV light and EPA could be a biocompatible coating for reduced bone bonding ability of Ti while promoting bone formation. 相似文献
66.
The APOE epsilon4 allele has been associated with unfavorable outcome after several types of acute brain injury, yet the biological mechanisms underlying this observation are poorly understood. Postmortem and experimental brain injury studies suggest the presence of increased amounts of apolipoprotein E (apoE) within the neuropil after acute brain injury. We assayed the concentration of apolipoprotein E in the cerebrospinal fluid (CSF) of non-injured controls and patients with traumatic brain injury (TBI) to determine whether differences exist, and if these differences correlate with injury severity and clinical outcome. CSF apoE and S100B, a marker of injury severity, were measured by enzyme linked immunosorbant assay. CSF was sampled from 27 traumatic brain injury patients (mean age 32, median 25, range 16-65 years) within 3 days of injury, and 28 controls (mean age 40, median 37, range 19-73 years). The TBI patients all had a Glasgow Coma Score (GCS) of less than eight (i.e., severe head injury). Clinical outcome was determined using the Glasgow Outcome Score (GOS). The average concentration of apoE in the CSF of controls was 12.4 mg/L (95% CI: 10.5-14.3 mg/L) and in TBI patients was 3.7 mg/L (95% CI: 2.1-4.1 mg/L; Mann-Whitney: p < 0.0001). In contrast, the concentration of S100B in the CSF of TBI patients was significantly higher than that of controls (Mann-Whitney: p < 0.0001). We speculate that apoE is retained within the parenchyma of the central nervous system in response to injury where in view of previous data, it may have a protective role. 相似文献
67.
K E Ruckh?berle J Petzold R Faber I Hakenbeck B Viehweg B Ruckh?berle J Forberg 《Zentralblatt für Gyn?kologie》1986,108(16):974-982
The authors are involved in a study in the field of nuclear medicine aimed at further clarifying the connection between premature delivery and placental insufficiency. They are particularly concerned with uteroplacental perfusion at the time when a trend is emerging toward premature birth, and with ways of treating this by exclusive therapy using betamimetics and/or additional maternal oxygen inhalation/additional maternal transcutaneous dorsal nerve stimulation (TNS). The significantly longer half-life periods of activity increase found at the time of hospitalization similar to pregnancies with intra-uterine fetal retardation, as compared with a normal control group, are interpreted as expressing a hemodynamic placental insufficiency and a risk of premature delivery. In contrast to exclusive betamimetic therapy, additional O2 inhalation/additional TNS significantly shorten the half-life period both in short-time and long-time tests. The better therapeutic effect on uteroplacental perfusion in cases of imminent premature delivery which is thus demonstrated can be seen also in an improved respiratory condition of the fetus as shown in a cardiotocogram. From a clinical point of view, the authors call attention to the clearly prolonged pregnancy periods regardless of the duration of gestation, at the time when a trend is emerging toward premature birth, as compared with exclusive betamimetic therapy, the duration of tocolysis/amount of betamimetic applied being the same. 相似文献
68.
69.
Depressed new neurons--adult hippocampal neurogenesis and a cellular plasticity hypothesis of major depression. 总被引:13,自引:0,他引:13
In a novel theory, a failure of adult hippocampal neurogenesis has been proposed to provide the biological and cellular basis of major depression. The as yet unresolved function of the new hippocampal neurons will have to be in the center of any attempt to prove this hypothesis. Only knowledge of normal functional relevance of new neurons will allow an assessment of their potential role in disturbed hippocampal function in depression; however, major depression is not primarily a hippocampal disorder. We therefore propose that consideration of the neurogenesis hypothesis of depression be the most prominent aspect of a more general cellular plasticity hypothesis. 相似文献
70.
Kronenberg G Wang LP Geraerts M Babu H Synowitz M Vicens P Lutsch G Glass R Yamaguchi M Baekelandt V Debyser Z Kettenmann H Kempermann G 《Brain structure & function》2007,212(1):19-35
Since reports that precursor cells in the adult subventricular zone (SVZ) contribute to regenerative neuro- and gliogenesis
in CA1, we wondered whether a similar route of migration might also exist under physiological conditions. Permanent labeling
of SVZ precursor cells with a lentiviral vector for green fluorescent protein did not reveal any migration from the SVZ into
CA1 in the intact murine brain. However, in a nestin-GFP reporter mouse we found proliferating cells within the corpus callosum/alveus
region expressing nestin and glial fibrillary acidic protein similar to precursor cells in the neighboring neurogenic region
of the adult dentate gyrus. Within 3 weeks of BrdU administration, BrdU-positive nestin-GFP-expressing protoplasmic astrocytes
emerged in CA1. Similar to precursor cells isolated from the dentate gyrus and the SVZ, nestin-GFP-expressing cells from corpus
callosum/alveus were self-renewing and multipotent in vitro, whereas cells isolated from CA1 were not. Nestin-GFP-expressing
cells in CA1 differentiated into postmitotic astrocytes characterized by S100β expression. No new neurons were found in CA1.
The number of nestin-GFP-expressing astrocytes in CA1 was increased by environmental enrichment. We conclude that astrogenesis
in CA1 is influenced by environmental conditions. However, SVZ precursor cells do not contribute to physiological cellular
plasticity in CA1. 相似文献