Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 11
    Keywords: brain ; RECEPTOR ; CELLS ; PATHWAY ; PATHWAYS ; GENE ; GENES ; RELEASE ; RESPONSES ; MECHANISM ; FREQUENCY ; hormone ; STRESS ; inactivation ; SIGNALING PATHWAY ; SIGNALING PATHWAYS ; glucocorticoid receptor ; LIVING CELLS ; RECEPTORS ; GLUCOCORTICOID-RECEPTOR ; ANTAGONIST ; rodent ; SUBCELLULAR-LOCALIZATION ; signaling ; NEURONS ; LIFE ; ENHANCEMENT ; ESTROGEN ; corticosteroid ; mineralocorticoid receptor ; LEVEL ; function ; alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor CA1 hippocampus ; glucocorticoid receptor knockout ; MICRODIALYSIS ; mineralocorticoid receptor knockout ; miniature excitatory postsynaptic current ; RAT HIPPOCAMPUS ; SYNAPSES
    Abstract: The adrenal hormone corticosterone transcriptionally regulates responsive genes in the rodent hippocampus through nuclear mineralocorticoid and glucocorticoid receptors. Via this genomic pathway the hormone alters properties of hippocampal cells slowly and for a prolonged period. Here we report that corticosterone also rapidly and reversibly changes hippocampal signaling. Stress levels of the hormone enhance the frequency of miniature excitatory postsynaptic potentials in CA1 pyramidal neurons and reduce paired-pulse facilitation, pointing to a hormone-dependent enhancement of glutamate-release probability. The rapid effect by corticosterone is accomplished through a nongenomic pathway involving membrane-located receptors. Unexpectedly, the rapid effect critically depends on the classical mineralocorticoid receptor, as evidenced by the effectiveness of agonists, antagonists, and brain-specific inactivation of the mineralocorticoid but not the glucocorticoid receptor gene. Rapid actions by corticosterone would allow the brain to change its function within minutes after stress-induced elevations of corticosteroid levels, in addition to responding later through gene-mediated signaling pathways
    Type of Publication: Journal article published
    PubMed ID: 16361444
    Signatur Availability
    BibTip Others were also interested in ...
  • 12
    Keywords: APOPTOSIS ; CELLS ; EXPRESSION ; CELL ; IN-VIVO ; MODEL ; PATHWAY ; PATHWAYS ; GENE ; GENES ; PROTEIN ; PROTEINS ; TISSUE ; MICE ; ACTIVATION ; INDUCTION ; TISSUES ; TARGET ; TRANSGENIC MICE ; SIGNAL-TRANSDUCTION ; p53 ; EPITHELIAL-CELLS ; PHENOTYPE ; C-MYC ; REGULATOR ; CYTOKINE ; RE ; INCREASE ; GLAND ; LEVEL ; TARGET GENES ; PREGNANCY ; mammary gland ; LACTATION ; PROLACTIN ; mammary ; GP130 ; Stat3 ; mammary epithelial cells ; ONCOSTATIN-M ; CYTOKINE SIGNALING-3 ; GENE DELETION ; Socs3
    Abstract: Suppressor of cytokine signalling (SOCS) proteins are critical attenuators of cytokine-mediated signalling in diverse tissues. To determine the importance of Socs3 in mammary development, we generated mice in which Socs3 was deleted in mammary epithelial cells. No overt phenotype was evident during pregnancy and lactation, indicating that Socs3 is not a key physiological regulator of prolactin signalling. However, Socs3-deficient mammary glands exhibited a profound increase in epithelial apoptosis and tissue remodelling, resulting in precocious involution. This phenotype was accompanied by augmented Stat3 activation and a marked increase in the level of c-myc. Moreover, induction of c-myc before weaning using an inducible transgenic model recapitulated the Socs3 phenotype, and elevated expression of likely c-myc target genes, E2F-1, Bax and p53, was observed. Our data establish Socs3 as a critical attenuator of pro-apoptotic pathways that act in the developing mammary gland and provide evidence that c-myc regulates apoptosis during involution
    Type of Publication: Journal article published
    PubMed ID: 17139252
    Signatur Availability
    BibTip Others were also interested in ...
  • 13
    Keywords: CELLS ; EXPRESSION ; BLOOD ; CELL ; SYSTEM ; GENE ; PROTEIN ; PROTEINS ; METABOLISM ; MICE ; COMPLEX ; FAMILY ; MEMBER ; MEMBERS ; knockout ; MOUSE ; NO ; IDENTIFICATION ; PROMOTER ; PLASMA ; MEMBRANE ; inactivation ; ADHESION ; CELL-ADHESION ; PLASMA-MEMBRANE ; Jun ; beta-catenin ; CRE RECOMBINASE ; PROTEIN INTERACTIONS ; CATENIN ; FOLLICLE ; E-cadherin ; ENDOCRINE ; FAMILIES ; INCREASE ; ADHESION MOLECULE UVOMORULIN ; GLAND ; cell adhesion ; development ; KNOCKOUT MICE ; ADHERENS JUNCTIONS ; USA ; LOSSES ; BARRIER ; CDNA CLONING ; MAINTENANCE ; Cre-loxP system ; FOLLICULAR CELLS ; KSP-CADHERIN ; SHAPE
    Abstract: We have conditionally inactivated the E-cadherin gene in the thyroid follicular cells of mouse embryo to unravel its role in thyroid development. We used the Cre-loxP system in which the Cre-recombinase was expressed under the control of the tissue-specific thyroglobulin promoter that becomes active at embryonic d 15. At postnatal d 7, thyroid follicle lumens in the knockout mice were about 30% smaller with respect to control mice and had an irregular shape. E-cadherin was almost completely absent in thyrocytes, beta-catenin was significantly reduced, whereas no change in gamma-catenin was detected. alpha-Catenin was also reduced on the cell plasma membrane. Despite the dramatic loss of E-cadherin and beta-catenin, cell-cell junctions were not affected, the distribution of tight junction proteins was unaltered, and no increase of thyroglobulin circulating in the blood was observed. In addition, we found that other members of the cadherin family, the R-cadherin and the Ksp-cadherin, were expressed in thyrocytes and that their membrane distribution was not altered in the E-cadherin conditional knockout mouse. Our results indicate that E-cadherin has a role in the development of the thyroid gland and in the expression of beta-catenin, but it is not essential for the maintenance of follicular cell adhesion
    Type of Publication: Journal article published
    PubMed ID: 17347311
    Signatur Availability
    BibTip Others were also interested in ...
  • 14
    Keywords: CELLS ; EXPRESSION ; CELL ; MODEL ; MODELS ; DEATH ; DISEASE ; liver ; GENE ; MICE ; COMPLEX ; COMPLEXES ; CEREBELLUM ; MIGRATION ; MOUSE MODEL ; ABNORMALITIES ; DEFECTS ; development ; MOUSE MODELS ; BIOGENESIS ; peroxisome ; DYSFUNCTION ; CORTICAL NEURONAL MIGRATION ; GRANULE CELLS ; neocortex ; NMDA RECEPTORS ; ZELLWEGER-SYNDROME
    Abstract: Defects in the formation of the cerebral cortex and the cerebellum are a prominent feature of the peroxisome biogenesis disorder Zellweger syndrome and in mouse models for this disease. The aim of the present study was to investigate the impact of liver and brain peroxisomes on neurodevelopment by analyzing mice with tissue-selective elimination of peroxisomes. To this end, Pex5-IoxP mice were bred with albumin/alpha-fetoprotein (Alfp)-Cre and nestin (Nes)-Cre mice. Local elimination of peroxisomes from the brain in Nes-Pex5 knockout mice caused a delay of cortical neuronal migration and of the formation of cerebellar folia and fissures. Migration of granule cells from the external granular layer was retarded, as was the polarization and branching of Purkinje cells, resulting in a less complex branching pattern and a smaller dendritic tree at P21. The Alfp-Pex5 knockout mice were affected differently, displaying a partial arrest of neuronal migration in the cerebral neopallium in the postnatal period despite of the incomplete elimination of peroxisomes from liver during embryonic development. Major abnormalities were seen in the formation of the cerebellum of these liver knockout mice, including hypotrophy, impaired foliation, a delay of granule cell migration, increased cell death, and stunted Purkinje cell arborization. In conclusion, these data demonstrate that absence of peroxisomal function both from liver and brain impairs cortical neuronal migration and maturation of the cerebellum, but different pathogenic mechanisms might be involved. (c) 2006 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 17075904
    Signatur Availability
    BibTip Others were also interested in ...
  • 15
    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
    Signatur Availability
    BibTip Others were also interested in ...
  • 16
    Keywords: RECEPTOR ; EXPRESSION ; CELL ; IN-VIVO ; DRUG ; MICE ; ACTIVATION ; CONTRAST ; LONG-TERM POTENTIATION ; MUTANT ; NO ; synaptic plasticity ; DELIVERY ; SUBUNITS ; sensitization ; RECEPTORS ; BEHAVIOR ; NEURONS ; conditioned place preference ; TECHNOLOGY ; USA ; TRANSMISSION ; SHORT-TERM ; NMDA RECEPTORS ; PLASTICITY ; AMPA RECEPTORS ; BEHAVIORAL SENSITIZATION ; VENTRAL TEGMENTAL AREA
    Abstract: Cocaine strengthens excitatory synapses onto midbrain dopamine neurons through the synaptic delivery of GluR1-containing AMPA receptors. This cocaine-evoked plasticity depends on NMDA receptor activation, but its behavioral significance in the context of addiction remains elusive. Here, we generated mice lacking the GluR1, GluR2, or NR1 receptor subunits selectively in dopamine neurons. We report that in midbrain slices of cocaine-treated mice, synaptic transmission was no longer strengthened when GluR1 or NR1 was abolished, while in the respective mice the drug still induced normal conditioned place preference and locomotor sensitization. In contrast, extinction of drug-seeking behavior was absent in mice lacking GluR1, while in the NR1 mutant mice reinstatement was abolished. In conclusion, cocaine-evoked synaptic plasticity does not mediate concurrent short-term behavioral effects of the drug but may initiate adaptive changes eventually leading to the persistence of drug-seeking behavior
    Type of Publication: Journal article published
    PubMed ID: 18701074
    Signatur Availability
    BibTip Others were also interested in ...
  • 17
    Keywords: brain ; RECEPTOR ; CELL ; Germany ; IN-VIVO ; MODEL ; MODELS ; VIVO ; SYSTEM ; TOOL ; METABOLISM ; MICE ; ACTIVATION ; RESPONSES ; MECHANISM ; mechanisms ; hippocampus ; MOUSE ; NERVOUS-SYSTEM ; DISRUPTION ; STRESS ; MUTATION ; DNA-BINDING ; MUTATIONS ; MOUSE MODEL ; glucocorticoid receptor ; DOMAINS ; DISSECTION ; review ; RE ; RESPONSIVENESS ; FOREBRAIN ; TECHNOLOGY ; LOSSES ; ENGLAND ; steroids ; STEROID-HORMONE RECEPTORS ; CRE RECOMBINASE ACTIVITY ; cortisol/corticosterone ; HPA axis
    Abstract: In the brain, glucocorticoids exert functions in neurogenesis, synaptic plasticity and behavioural responses, as well as in the control of hypothalamic-pituitary-adrenal axis activity. The generation of mice harbouring germline mutations that result either in loss or in gain of glucocorticoid receptor function provided a useful tool for understanding the role of glucocorticoids in the brain in vivo. The improvement of genomic technologies additionally allowed the establishment of mouse models with function-selective point mutations of the receptor as well as the generation of mice harbouring spatially and/or temporally restricted loss of glucocorticoid receptor, specifically within the brain. These models will provide the opportunity to better understand the mechanisms involved in glucocorticoid signalling within the nervous system
    Type of Publication: Journal article published
    PubMed ID: 18513206
    Signatur Availability
    BibTip Others were also interested in ...
  • 18
    Keywords: RECEPTOR ; APOPTOSIS ; CELLS ; GROWTH ; CELL ; MODEL ; MODELS ; GENE ; transcription ; METABOLISM ; DIFFERENTIATION ; MICE ; ACTIVATION ; DNA ; MECHANISM ; MARKER ; primary ; INDUCTION ; KERATINOCYTES ; mechanisms ; SKIN ; MATURATION ; MOUSE ; NUMBER ; DNA-BINDING ; SIGNALING PATHWAY ; epidermis ; ARCHITECTURE ; desmosomes ; USA ; LOSSES ; HOMEOSTASIS ; BARRIER ; CASPASE-14 ; EPIDERMAL-KERATINOCYTES ; FETAL MOUSE
    Abstract: To investigate the contribution of the glucocorticoid receptor (GR) in skin development and the mechanisms underlying this function, we have analyzed two mouse models in which GR has been functionally inactivated: the knockout GR(-/-) mice and the dimerization mutant GR(dim/dim) that mediates defective DNA binding-dependent transcription. Because GR null mice die perinatally, we evaluated skin architecture of late embryos by histological, immunohistochemical, and electron microscopy studies. Loss of function of GR resulted in incomplete epidermal stratification with dramatically abnormal differentiation of GR(-/-), but not GR(+/-) embryos, as demonstrated by the lack of loricrin, filaggrin, and involucrin markers. Skin sections of GR(-/-) embryos revealed edematous basal and lower spinous cells, and electron micrographs showed increased intercellular spaces between keratinocytes and reduced number of desmosomes. The absent terminal differentiation in GR(-/-) embryos correlated with an impaired activation of caspase-14, which is required for the processing of profilaggrin into filaggrin at late embryo stages. Accordingly, the skin barrier competence was severely compromised in GR(-/-) embryos. Cultured mouse primary keratinocytes from GR(-/-) mice formed colonies with cells of heterogeneous size and morphology that showed increased growth and apoptosis, indicating that GR regulates these processes in a cell-autonomous manner. The activity of ERK1/2 was constitutively augmented in GR(-/-) skin and mouse primary keratinocytes relative to wild type, which suggests that GR modulates skin homeostasis, at least partially, by antagonizing ERK function. Moreover, the epidermis of GR(+/dim) and GR(dim/dim) embryos appeared normal, thus suggesting that DNA-binding-independent actions of GR are sufficient to mediate epidermal and hair follicle development during embryogenesis
    Type of Publication: Journal article published
    PubMed ID: 18039792
    Signatur Availability
    BibTip Others were also interested in ...
  • 19
    Keywords: RECEPTOR ; APOPTOSIS ; CANCER ; CELLS ; GROWTH ; IN-VITRO ; tumor ; carcinoma ; CELL ; human ; IN-VIVO ; MODEL ; MODELS ; PATHWAY ; VITRO ; SYSTEM ; incidence ; GENE ; MICE ; PATIENT ; MECHANISM ; primary ; SKIN ; SUPPRESSION ; PROGRESSION ; NUMBER ; MELANOMA ; CANCER-CELLS ; RECEPTORS ; CHILDHOOD NEUROBLASTOMAS ; APOPTOSIS-INDUCING LIGAND ; AGENT ; CELL CARCINOMA ; RE ; TUMOR-GROWTH ; INCREASE ; CASPASE-8 ; C-FLIP ; SUPPRESSOR ; death receptor ; USA ; MEDICINE ; anoikis
    Abstract: TRAIL is a promising anticancer agent due to its ability to selectively induce apoptosis in established tumor cell lines but not nontransformed cells. Herein, we demonstrate a role for the apoptosis-inducing TRAIL receptor (TRAIL-R) as a metastasis suppressor. Although mouse models employing tumor transplantation have shown that TRAIL can reduce tumor growth, autochthonous tumor models have generated conflicting results with respect to the physiological role of the TRAIL system during tumorigenesis. We used a multistage model of squamous cell carcinoma to examine the role of TRAIL-R throughout all steps of tumor development. DMBA/TPA-treated TRAIL-R-deficient mice showed neither an increase in number or growth rate of benign papillomas nor an increase in the rate of progression to squamous cell carcinoma. However, metastasis to lymph nodes was significantly enhanced, indicating a role for TRAIL-R specifically in the suppression of metastasis. We also found that adherent TRAIL-R-expressing skin carcinoma cells were TRAIL resistant in vitro but were sensitized to TRAIL upon detachment by inactivation of the ERK signaling pathway. As detachment from the primary tumor is an obligatory step in metastasis, this provides a possible mechanism by which TRAIL-R could inhibit metastasis. Hence, treatment of cancer patients with agonists of the apoptosis-inducing receptors for TRAIL may prove useful in reducing the incidence of metastasis
    Type of Publication: Journal article published
    PubMed ID: 18079967
    Signatur Availability
    BibTip Others were also interested in ...
  • 20
    Keywords: APOPTOSIS ; CELLS ; GROWTH ; proliferation ; SURVIVAL ; CELL ; Germany ; INHIBITION ; SYSTEM ; DEATH ; GENE ; GENES ; RNA ; transcription ; MICE ; ACTIVATION ; TRANSCRIPTION FACTOR ; INDUCTION ; hippocampus ; NERVOUS-SYSTEM ; TRANSCRIPTIONAL ACTIVITY ; DISRUPTION ; CELL-DEATH ; STRESS ; inactivation ; p53 ; STRATEGIES ; INTERACTS ; HEALTHY ; molecular ; ADULT ; RE ; FACTOR TIF-IA ; NEURONS ; ABLATION ; LEVEL ; cell death ; nucleolus ; RNA polymerase I ; progenitor ; INDUCE ; USA ; LOSSES ; neurodegeneration ; PROGENITORS ; DEGENERATION ; NOV ; response ; synthesis ; POLYMERASE ; STATE ; RNA-POLYMERASE ; neural progenitors ; rRNA transcription ; TRANSCRIPTION ACTIVITY
    Abstract: Transcription of rRNA genes is essential for maintaining nucleolar integrity, a hallmark for the healthy state and proliferation rate of a cell. Inhibition of rRNA synthesis leads to disintegration of the nucleolus, elevated levels of p53, and induction of cell suicide, identifying the nucleolus as a critical stress sensor. Whether deregulation of rRNA synthesis is causally involved in neurodegeneration by promoting cell death and/or by inhibiting cellular growth has however not been addressed. The transcription factor TIF-IA plays a central role in mammalian rRNA synthesis, regulating the transcriptional activity of RNA polymerase I. To investigate the consequences of nucleolar perturbation in the nervous system, we have chosen to specifically ablate the gene encoding the transcription factor TIF-IA in two different contexts: neural progenitors and hippocampal neurons. Here, we show that ablation of TIF-IA leads to impaired nucleolar activity and results in increased levels of the proapoptotic transcription factor p53 in both neural progenitors and hippocampal neurons but induces rapid apoptosis only in neural progenitors. Nondividing cells of the adult hippocampus are more refractory to loss of rRNA transcription and face a protracted degeneration. Our study provides an unexploited strategy to initiate neurodegeneration based on perturbation of nucleolar function and underscores a novel perspective to study the cellular and molecular changes involved in the neurodegenerative processes
    Type of Publication: Journal article published
    PubMed ID: 19036968
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...