排序方式: 共有55条查询结果,搜索用时 15 毫秒
1.
Sara Proietti Alessandra Cucina Gabriella Dobrowolny Fabrizio D'Anselmi Simona Dinicola Maria Grazia Masiello Alessia Pasqualato Alessandro Palombo Veronica Morini Russel J. Reiter Mariano Bizzarri 《Journal of pineal research》2014,57(1):120-129
Compelling evidence demonstrated that melatonin increases p53 activity in cancer cells. p53 undergoes acetylation to be stabilized and activated for driving cells destined for apoptosis/growth inhibition. Over‐expression of p300 induces p53 acetylation, leading to cell growth arrest by increasing p21 expression. In turn, p53 activation is mainly regulated in the nucleus by MDM2. MDM2 also acts as E3 ubiquitin ligase, promoting the proteasome‐dependent p53 degradation. MDM2 entry into the nucleus is finely tuned by two different modulations: the ribosomal protein L11, acts by sequestering MDM2 in the cytosol, whereas the PI3K‐AkT‐dependent MDM2 phosphorylation is mandatory for MDM2 translocation across the nuclear membrane. In addition, MDM2‐dependent targeting of p53 is regulated in a nonlinear fashion by MDM2/MDMX interplay. Melatonin induces both cell growth inhibition and apoptosis in MCF7 breast cancer cells. We previously reported that this effect is associated with reduced MDM2 levels and increased p53 activity. Herein, we demonstrated that melatonin drastically down‐regulates MDM2 gene expression and inhibits MDM2 shuttling into the nucleus, given that melatonin increases L11 and inhibits Akt‐PI3K‐dependent MDM2 phosphorylation. Melatonin induces a 3‐fold increase in both MDMX and p300 levels, decreasing simultaneously Sirt1, a specific inhibitor of p300 activity. Consequently, melatonin‐treated cells display significantly higher values of both p53 and acetylated p53. Thus, a 15‐fold increase in p21 levels was observed in melatonin‐treated cancer cells. Our results provide evidence that melatonin enhances p53 acetylation by modulating the MDM2/MDMX/p300 pathway, disclosing new insights for understanding its anticancer effect. 相似文献
2.
Bernstein HG Brisch R Ogonlade V Heinemann A Baumann B Arendt T Dobrowolny H Bogerts B Lüth HJ 《Journal of chemical neuroanatomy》2004,27(4):247-250
There is a remarkable discrepancy between biochemical and cell morphological findings with regard to the presence of NADPH diaphorase/neuronal nitric oxide synthase (NOS) in the primate septal area. Whereas considerable concentrations of neuronal nitric oxide synthase and high enzyme activities have been measured in postmortem human septal nuclei, histochemical studies were either unable to detect any nitric oxide synthase immunoreactivity in primate septal neurons, or found only a very few nitrergic neurons in this region. This study aimed to investigate the possible presence of nitrergic neurons in human the septal region in greater detail. After having studied a total of 16 postmortem human brains we conclude that the immunohistochemical demonstration of nitric oxide synthase in human septal neurons is largely dependent on the mode of tissue handling: in brain specimens which were fixed en-bloc with paraffin and embedded in paraplast, nitric oxide synthase immunoreactivity is barely detectable, whereas a satisfying immunostaining is obtained on free-floating frozen sections after an immersion–fixation with 4% paraformaldehyde and 0.5% glutaraldehyde, followed by sucrose protection of the specimens. We show herein that there are indeed nitric oxide synthase-containing neurons in the human septum, thus supporting results from previous biochemical studies. 相似文献
3.
Ralf Brisch Hans-Gert Bernstein Renate Stauch Henrik Dobrowolny Dieter Krell Kurt Truebner Gabriela Meyer-Lotz Hendrik Bielau Johann Steiner Siegfried Kropf Tomasz Gos Peter Danos Bernhard Bogerts 《Psychiatry Research: Neuroimaging》2008,164(3):265-273
Structural and functional pathology of limbic structures including the hippocampus are frequently replicated in schizophrenia. Although the fornix is the main afferent system of the hippocampus to the septal nuclei and the hypothalamus (especially the mammillary bodies), relatively few studies have investigated structural changes of the fornix in schizophrenia. We measured the volume of the fornix in post-mortem brains in 19 patients with schizophrenia, 9 patients with bipolar disorder, 7 patients with unipolar depression, and 14 control subjects by planimetry of serial sections. The volumes, the mean cross-sectional areas, and the anterior to posterior distances of the fornix did not differ among patients with schizophrenia, bipolar disorder, unipolar depression, and control subjects. No lateralization existed between the right and the left fornices in among patients in the diagnostic groups and the control subjects. The fornix does not show morphometrical abnormalities in patients with schizophrenia, bipolar disorder and unipolar depression compared with control subjects, which might indicate that the fornix is not a primary focus of structural changes in these diseases. 相似文献
4.
Hans-Gert Bernstein Anna Ortmann Henrik Dobrowolny Johann Steiner Ralf Brisch Tomasz Gos Bernhard Bogerts 《European archives of psychiatry and clinical neuroscience》2016,266(1):25-33
Multiple brain structural abnormalities have been reported in schizophrenia and major depressive disorder. A majority of disease-affected brain regions act as relay nodes within neural networks, which are known to be impaired in neuropsychiatric diseases. One of these regions is the claustrum, which has the highest connectivity in the human brain by regional volume. Its possible involvement in disturbed connectivity is yet incompletely explored, however. The present study aimed at searching for possible structural deviations of the claustrum in neuropsychiatric disorders. We found bilaterally reduced claustral volumes both in schizophrenia and in major depressive disorder. These structural impairments may have different, disease-related consequences: In patients with schizophrenia, they may contribute to sensory processing impairments, and in patients with major depressive disorder to disturbances in salience. 相似文献
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Brisch R Bernstein HG Krell D Stauch R Trübner K Dobrowolny H Kropf S Bielau H Bogerts B 《European archives of psychiatry and clinical neuroscience》2007,257(3):140-148
MRI and post-mortem studies indicate an increased prevalence of cavum septi pellucidi (CSP) in schizophrenia and affective
disorder. The aim of this study was to characterize the CSP and the septal tissue among patients with schizophrenia, patients
with affective disorder, and control subjects. The volumes of CSP and septal tissue were measured in post-mortem brains in
42 patients with schizophrenia, 14 patients with affective disorder, and 17 normal control cases by planimetry of serial sections.
Enlargements of CSP (>100 mm3) were found in eight of the 42 (19%) patients with schizophrenia. There were no significant differences in CSP volumes between
patients with affective disorder and controls. Enlarged CSP in schizophrenia were not associated with reduced septal tissue
volumes. By contrast, a significant positive correlation between volumes of CSP and septal tissue volumes in patients with
schizophrenia (P = 0.03) and in control cases (P < 0.01) was found, but not in patients with affective disorder (P = 0.53). The finding of enlarged CSP in schizophrenia strongly supports the hypothesis of an early developmental abnormality
in this key structure of the limbic system. 相似文献
7.
Introduction The hypo-glutamatergic hypothesis of schizophrenia is based on clinical similarities between schizophrenia and phencyclidine
(PCP)-induced psychosis in mentally healthy humans. Sensorimotor gating, as measured by prepulse inhibition (PPI) of the acoustic
startle response (ASR), is impaired in schizophrenic patients. In animals, noncompetitive N-methyl-d-aspartate (NMDA) antagonists such as PCP disrupt PPI in a way that resembles the defect seen in schizophrenia. In a previous
study with inbred mouse strains, low PPI levels have been demonstrated in CPB-K mice possessing low levels of hippocampal
NMDA receptor densities. The present study was performed to test whether the low magnitude of PPI in CPB-K mice can be reversed
by the atypical antipsychotic drug clozapine (CLZ).
Results Before any treatment, CPB-K mice displayed a significant (p < 0.001) lower level in PPI and a significant (p < 0.001) higher ASR when compared to BALB/cJ mice known to have high hippocampal NMDA receptor densities. Acute and subchronic
effects of a 2-week treatment with CLZ at daily doses of 5 and 10 mg/kg intraperitoneally, respectively, did not reveal any
significant alteration of PPI levels in CPB-K mice. Nevertheless, the examination of motor behavior during nonstimulus trials
provided a positive control for the drug’s effectiveness.
Conclusion In summary, (1) this study confirmed our working hypothesis: Lower levels of hippocampal glutamatergic receptor densities
correspond to lower sensorimotor gating in CPB-K mice, and (2) acute or subchronic treatment with CLZ did not elevate low
PPI levels in CPB-K mice. Thus, further experiments will concentrate on other antipsychotic drugs to prove the predictive
validity of this animal model. 相似文献
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Panther P Nullmeier S Dobrowolny H Schwegler H Wolf R 《Behavioural brain research》2012,230(1):215-228
Schizophrenia is characterized by disturbances in social behavior, sensorimotor gating and cognitive function, that are discussed to be caused by a termination of different transmitter systems. Beside morphological alterations in cortical and subcortical areas reduced AMPA- NMDA-, 5-HT2-receptor densities and increased 5-HT1-receptor densities are found in the hippocampus.The two inbred mouse strains CPB-K and BALB/cJ are known to display considerable differences in cognitive function and prepulse inhibition, a stable marker of sensorimotor gating. Furthermore, CPB-K mice exhibit lower NMDA-, AMPA- and increased 5-HT-receptor densities in the hippocampus as compared to BALB/cJ mice. We investigated both mouse strains in social interaction test for differences in social behavior and with immuncytochemical approaches for alterations of dopaminergic and serotonergic parameters. Our results can be summarized as follows: compared to BALB/cJ, CPB-K mice showed:(1) significantly reduced traveling distance and number of contacts in social interaction test, (2) differences in the number of serotonin transporter-immunoreactive neurons and volume of raphe nuclei and a lower serotonergic fiber density in the ventral and dorsal hippocampal subfields CA1 and CA3, (3) no alterations of dopaminergic markers like neuron number, neuron density and volume in subregions of substantia nigra and ventral tegmental area, but a significantly higher dopaminergic fiber density in the dorsal hippocampus, the ventral hippocampus of CA1 and gyrus dentatus, (4) no significant differences in serotonergic and dopaminergic fiber densities in the amygdala.Based on our results and previous studies, CPB-K mice compared to BALB/cJ may serve as an important model to understand the interaction of the serotonergic and dopaminergic system and their impact on sensorimotor gating and cognitive function as related to neuropsychiatric disorders like schizophrenia. 相似文献
10.
Hans-Gert Bernstein Karl-Heinz Smalla Diana Dürrschmidt Gerburg Keilhoff Henrik Dobrowolny Johann Steiner Andrea Schmitt Michael R. Kreutz Bernhard Bogerts 《Neuromolecular medicine》2012,14(4):270-280
Prohibitin has previously been implicated in the synaptic pathology of schizophrenia. The recently discovered abundant expression of prohibitin in human prefrontal oligodendrocytes raises the issue, whether this protein might also be part of the well-known white matter abnormalities in schizophrenia. Hence, post-mortem brains of ten patients with schizophrenia and ten matched control cases were investigated. Using a direct, 3D-counting technique we morphometrically analyzed the number and density of prohibitin-immunoreactive oligodendroglial cells in the left and right dorsolateral, anterior cingulate, and orbitofrontal cortex white matter. Additionally, we studied the prohibitin expression in different neuronal and non-neuronal cell populations in rat cell cultures. We could confirm the strong expression of prohibitin in oligodendrocytes. Intracellularly, the protein was localized to mitochondria and some cell nuclei. In schizophrenia, the numerical density of prohibitin-expressing oligodendrocytes was significantly increased in the right dorsolateral white matter area. Taking into consideration the dual intracellular localization of prohibitin in oligodendrocyte mitochondria and cell nuclei, one may suggest an involvement of the protein in mitochondrial dysfunction and/or cycle abnormalities in schizophrenia. 相似文献