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  • 1
    Keywords: brain ; EXPRESSION ; Germany ; human ; GENE ; transcription ; MICE ; PATIENT ; ACTIVATION ; TRANSCRIPTION FACTOR ; MARKER ; PHOSPHORYLATION ; ASSOCIATION ; polymorphism ; CAMP ; ELEMENT-BINDING PROTEIN ; PATTERNS ; CYCLIC-AMP ; molecular ; PATTERN ; LIGHT ; analysis ; MEDICINE ; CIRCADIAN CLOCK ; MAJOR DEPRESSION ; SUPRACHIASMATIC-NUCLEI
    Abstract: Activation of the transcription factor CREB by Ser142 phosphorylation is implicated in synchronizing circadian rhythmicity, which is disturbed in many depressive patients. Hence, one could assume that emotional behaviour and neuroendocrinological markers would be altered in CREBS142A mice, in which serine 142 is replaced by alanine, preventing phosphorylation at this residue. Moreover, associations of CREB Ser142 and seasonal affective disorder (SAD) might be detectable by the analysis of single-nucleotide polymorphisms (SNPs) in the CREB gene close to the Ser142 residue in SAD patients. However, neither CREBS142A mice demonstrate features of depression, nor there is evidence for an association of SAD with the CREB genotypes. Nevertheless, in humans there is an association of a global seasonality score and circadian rhythmicity with the CREB genotypes in healthy control probands, but not SAD patients. This parallels the phenotype of CREBS142A mice, presenting alterations of circadian rhythm and light-induced entrainment. Thus it is reasonable to assume that CREB Ser142 represents a molecular switch in mice and men, which is responsible for the (dys)regulation of circadian rhythms. (C) 2007 Elsevier Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 17574346
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  • 2
    Keywords: brain ; RECEPTOR ; EXPRESSION ; Germany ; MODEL ; MODELS ; SYSTEM ; EXPOSURE ; GENE ; PROTEIN ; MICE ; PATIENT ; MECHANISM ; MESSENGER-RNA ; RECEPTOR EXPRESSION ; chromosome ; MOUSE ; TRANSGENIC MICE ; hormone ; YEAST ; STRESS ; PATHOGENESIS ; DNA-BINDING ; Jun ; glucocorticoid receptor ; sensitivity ; BEHAVIOR ; OVEREXPRESSION ; GLUCOCORTICOID-RECEPTOR ; signaling ; molecular ; regulation ; KNOCKOUT MICE ; NEUROTROPHIC FACTOR ; FOREBRAIN ; RAT HIPPOCAMPUS ; depression ; DEXAMETHASONE-CRH TEST ; helplessness
    Abstract: Altered glucocorticoid receptor (GR) signaling is a postulated mechanism for the pathogenesis of major depression. To mimic the human situation of altered GR function claimed for depression, we generated mouse strains that underexpress or overexpress GR, but maintain the regulatory genetic context controlling the GR gene. To achieve this goal, we used the following: (1) GR-heterozygous mutant mice (GR(+/-)) with a 50% GRgene dose reduction, and (2) mice overexpressingGR by a yeast artificial chromosome resulting in a twofold gene dose elevation. GR(+/-) mice exhibit normal baseline behaviors but demonstrate increased helplessness after stress exposure, a behavioral correlate of depression in mice. Similar to depressed patients, GR(+/-) mice have a disinhibited hypothalamic-pituitary-adrenal (HPA) system and a pathological dexamethasone/corticotropin-releasing hormone test. Thus, they represent a murine depression model with good face and construct validity. Overexpression of GR in mice evokes reduced helplessness after stress exposure, and an enhanced HPA system feedback regulation. Therefore, they may represent a model for a stress-resistant strain. These mouse models can now be used to study biological changes underlying the pathogenesis of depressive disorders. As a first potential molecular correlate for such changes, we identified a downregulation of BDNF protein content in the hippocampus of GR+/- mice, which is in agreement with the so-called neurotrophin hypothesis of depression
    Type of Publication: Journal article published
    PubMed ID: 15987954
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  • 3
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The sigma1 (σ1) receptor exerts a potent neuromodulatory role in the brain with relevant consequences in memory processes, response to stress, depression and pharmacodependence. Its precise endogenous ligand is not yet identified but the σ1 receptor appears to be one target for the nongenomic rapid effects of neuroactive steroids in the brain. The aim of the present study was to establish whether differences in σ1 receptor-mediated behaviours could be observed among mouse strains, in relation with differences in either σ1 receptor expression or steroid levels. The σ1-receptor immunohistochemical distribution appeared similar between Swiss and C57BL/6 strains in all the brain structures examined. The levels of in vivo[3H](+)-SKF-10 047 binding to σ1 receptors were lower in Swiss than in C57BL/6. Adrenalectomy/castration significantly increased [3H](+)-SKF-10 047 binding only in Swiss. The behavioural efficacy of the selective σ1 agonists igmesine and PRE-084 – reversion of the scopolamine-induced amnesia in the passive avoidance test; diminution of the immobility duration in the forced swimming test – were significantly higher in C57BL/6 than in Swiss. Steroid levels were measured in the brain in basal conditions and after stress. C57BL/6 mice presented in both conditions, the lowest progesterone levels, this steroid acting as an endogenous σ1 antagonist. Collectively, the results suggested that strain differences in neuroactive steroid and particularly, progesterone, biosynthesis and sensitivity may contribute to the differential behavioural efficacy of σ1-receptor ligands. Noteworthy, these observations are coherent with strain differences observed in the intensity of cocaine-induced reward properties, known to critically involve the σ1 receptor.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The dentate gyrus is one of the few areas of the adult brain that continues to produce neurons and to express the embryonic polysialylated isoforms of neuronal cell adhesion molecules (PSA-NCAM). The stress hormone corticosterone exerts a complex modulation on neurogenesis and PSA-NCAM, and previous studies have shown that mature granule cells require corticosterone for their survival. Thus, the aim of our work was to investigate the respective role of the different corticosteroid receptors on these three parameters in adrenalectomized rats. It was found that treatment with a low dose of the mineralocorticoid receptor agonist, aldosterone, prevents only the adrenalectomy-induced increase in cell death. Treatment with a higher dose of aldosterone normalized cell proliferation whereas PSA-NCAM expression was normalized only by treatment with the glucocorticoid receptor agonist, RU 28362. It is concluded that stimulation of the mineralocorticoid receptor is sufficient to mediate the effects of corticosterone on neurogenesis and to protect mature cells from cell death whereas stimulation of the glucocorticoid receptor is necessary to modulate PSA-NCAM expression.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1574-695X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: In response to an increase in the incidence in invasive meningococcal disease (IMD) due to Neisseria meningitidis, a system of hospital- and laboratory-based surveillance was used in a prospective epidemiological and clinical assessment of IMD in children 0–13 years of age hospitalized in the Athens area between 1 January 1999 and 31 December 2000. The annual incidence of laboratory-confirmed disease was 10.2/100,000. Serogroup B strains were predominant. There was a sharp decrease in serogroup C from 19% of cases in 1999 to 3% in 2000 (P=0.013). Of note was the emergence of serogroup A responsible for 7% of the cases. The overall case fatality rate was 4.5%, but 2.8% for microbiologically confirmed cases. A remarkable decrease in disease severity assessed by admissions to intensive care units was noted during the second study year. Polymerase chain reaction-based methods for detection of meningococcal DNA were the sole positive laboratory test in 45% of the cases and the only test on which serogroup determination was based in 52% of groupable cases. The epidemiological and clinical profile of meningococcal disease appears to be rapidly evolving and close monitoring is required particularly for input into decisions regarding use of meningococcal vaccines.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 427 (2004), S. 378-378 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Eurodoc is a European federation of national organizations that represent young researchers in their respective countries. It aims to give a voice to PhD candidates, postdoctoral fellows and other junior researchers in European policy-making processes and to improve their working conditions. To ...
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1468-2982
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Twenty-four hour ECG Holter and blood-pressure monitorings were performed in eight patients suffering from cluster headache. Spectral analysis of heart-rate fluctuation was used to assess the autonomic balance under basal conditions, after head-up tilt, and during a spontaneous attack. Normal autonomic balance was found at rest and during sympathetic activation obtained with head-up tilt in the interparoxysmal period. Before the onset of headache, an increase in the low-frequency (LF) component of the power spectrum was apparent in all patients. This sign of sympathetic activation was followed by an increase in the high-frequency (HF) component that developed about 2000 beats after the onset of headache and rapidly overcame the LF component until the end of pain. Significant differences were found when comparing the spectral parameters [total spectral values (TP), power of the LF and HF components and LF/HF ratio] obtained before, during and after headache. During the attack, blood pressure increased and heart rate decreased in all subjects. There appears to be a primary activation of both sympathetic and parasympathetic functions in cluster headache attacks. The sympathetic component seems to be involved mostly in the development of the attack, whereas the parasympathetic activation seems to occur, following the onset of the attack, independently of the pain.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Although it has been postulated that adult neurogenesis, i.e. the generation of functional neurons from progenitor cells in the mammalian brain, is involved in both the pathogenesis of depressive disorders and the therapeutic effect of antidepressant drugs, its regulation is still poorly understood. Nitric oxide, a gaseous messenger molecule, represents a possible modulating agent as it is involved in learning and memory formation as well as synapto- and morphogenesis. Here we investigated whether adult neurogenesis is altered in mice lacking endothelial nitric oxide synthase (NOS-III). Compared to wild-type littermates, NOS-III-deficient mice showed a significant reduction in neuronal progenitor cell proliferation in the dentate gyrus, suggesting a role for NOS-III in the stimulation of neuroneogenesis. NeuN, β-III-tubulin and GFAP double-immunolabelling demonstrated that proliferating progenitor cells differentiate preferentially into neurons but not into astrocytes. However, when the survival rate of newly formed cells was examined no difference between wild-type and NOS-III knockout mice was found, suggesting that NOS-III selectively exerts its effects on the proliferation of progenitor cells. This might be mediated by a decrease in vascular endothelial growth factor (VEGF) transcripts in the hippocampus of knockout animals. At the behavioural level, while NOS-III knockout mice displayed better and faster learning in a learned helplessness paradigm, no depression-like behaviours were observed. In conclusion, our results indicated that NOS-III is involved in the proliferation of neuronal progenitor cells, although behavioural analysis does not provide evidence for a pro-depressive effect of reduced neuroneogenesis.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1573-0964
    Source: Springer Online Journal Archives 1860-2000
    Topics: Natural Sciences in General , Philosophy
    Notes: Abstract A rigorous extension of the full Lorentz group is found which is parameterized by interframe velocities v(t) and which reduces to Special Relativity for acceleration-free cases and to Galilean relativity for low velocity cases. Full group properties are exhibited. Four-momentum is defined and particle masses are shown to be invariants. Four-force is introduced and pseudoforces are shown to enter the equations of particle dynamics. Maxwell's equations are shown to take on pseudocurrent terms in accelerating frames. A four-vector Green function solution to the modified Maxwell equations is presented. Finally, a discussion is offered concerning philosophical questions such as the operational definition of time.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 0197-8462
    Keywords: Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Type of Medium: Electronic Resource
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