The Experts below are selected from a list of 13998 Experts worldwide ranked by ideXlab platform
Urban Lendahl - One of the best experts on this subject based on the ideXlab platform.
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notch signaling regulates platelet derived growth factor receptor β expression in vascular smooth muscle cells
Circulation Research, 2008Co-Authors: Shaobo Jin, Emil M. Hansson, Saara Tikka, Fredrik Lanner, Cecilia Sahlgren, Filip Farnebo, Marc Baumann, Hannu Kalimo, Urban LendahlAbstract:Notch signaling is critically important for proper architecture of the vascular system, and mutations in NOTCH3 are associated with CADASIL, a stroke and Dementia Syndrome with vascular smooth muscle cell (VSMC) dysfunction. In this report, we link Notch signaling to platelet-derived growth factor (PDGF) signaling, a key determinant of VSMC biology, and show that PDGF receptor (PDGFR)-beta is a novel immediate Notch target gene. PDGFR-beta expression was upregulated by Notch ligand induction or by activated forms of the Notch receptor. Moreover, upregulation of PDGFR-beta expression in response to Notch activation critically required the Notch signal integrator CSL. In primary VSMCs, PDGFR-beta expression was robustly upregulated by Notch signaling, leading to an augmented intracellular response to PDGF stimulation. In newborn Notch3-deficient mice, PDGFR-beta expression was strongly reduced in the VSMCs that later develop an aberrant morphology. In keeping with this, PDGFR-beta upregulation in response to Notch activation was reduced also in Notch3-deficient embryonic stem cells. Finally, in VSMCs from a CADASIL patient carrying a NOTCH3 missense mutation, upregulation of PDGFR-beta mRNA and protein in response to ligand-induced Notch activation was significantly reduced. In sum, these data reveal a hierarchy for 2 important signaling systems, Notch and PDGF, in the vasculature and provide insights into how dysregulated Notch signaling perturbs VSMC differentiation and function.
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notch signaling regulates platelet derived growth factor receptor β expression in vascular smooth muscle cells
Circulation Research, 2008Co-Authors: Emil M. Hansson, Saara Tikka, Fredrik Lanner, Cecilia Sahlgren, Filip Farnebo, Marc Baumann, Hannu Kalimo, Urban LendahlAbstract:Notch signaling is critically important for proper architecture of the vascular system, and mutations in NOTCH3 are associated with CADASIL, a stroke and Dementia Syndrome with vascular smooth muscle cell (VSMC) dysfunction. In this report, we link Notch signaling to platelet-derived growth factor (PDGF) signaling, a key determinant of VSMC biology, and show that PDGF receptor ( PDGFR )-β is a novel immediate Notch target gene. PDGFR -β expression was upregulated by Notch ligand induction or by activated forms of the Notch receptor. Moreover, upregulation of PDGFR -β expression in response to Notch activation critically required the Notch signal integrator CSL. In primary VSMCs, PDGFR -β expression was robustly upregulated by Notch signaling, leading to an augmented intracellular response to PDGF stimulation. In newborn Notch3 -deficient mice, PDGFR-β expression was strongly reduced in the VSMCs that later develop an aberrant morphology. In keeping with this, PDGFR-β upregulation in response to Notch activation was reduced also in Notch3 -deficient embryonic stem cells. Finally, in VSMCs from a CADASIL patient carrying a NOTCH3 missense mutation, upregulation of PDGFR -β mRNA and protein in response to ligand-induced Notch activation was significantly reduced. In sum, these data reveal a hierarchy for 2 important signaling systems, Notch and PDGF, in the vasculature and provide insights into how dysregulated Notch signaling perturbs VSMC differentiation and function.
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Mouse Notch 3 expression in the pre- and postnatal brain: relationship to the stroke and Dementia Syndrome CADASIL.
Experimental cell research, 2002Co-Authors: Nilima Prakash, Emil M. Hansson, Christer Betsholtz, Thimios A. Mitsiadis, Urban LendahlAbstract:Mutations in the human Notch 3 gene cause the vascular stroke and Dementia Syndrome CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) characterized by degeneration of vascular smooth muscle cells and multiple small infarcts in the white and deep gray matter of the brain. Here we have analyzed the expression pattern of the Notch 3 gene in the pre- and postnatal mouse brain. Prenatal Notch 3 expression is restricted to a scattered population of cells within the vessel wall of all major blood vessels in the developing embryo, including those that form the perineural vascular plexus. Expression in the postnatal brain is confined to a scattered cell population within the vessel wall of small to medium-sized penetrating arteries, which are the vessel type primarily affected in CADASIL patients. In contrast, no expression was observed in capillaries and veins. Notch 3 is most likely expressed in a subset of vascular smooth muscle cells, and the expression pattern of one of the Notch ligands, Serrate 1, was very similar to that observed for Notch 3. The Notch 3 expressing pattern was not significantly altered in platelet-derived growth factor B- (PDGF-B) deficient mouse embryos, demonstrating that Notch 3 expression is not under direct control of PDGF-B. These data show that Notch 3 expression is conserved between mouse and human and suggest that the mouse is a valid system for analysis of CADASIL.
Michael Hornberger - One of the best experts on this subject based on the ideXlab platform.
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common and unique gray matter correlates of episodic memory dysfunction in frontotemporal Dementia and alzheimer s disease
Human Brain Mapping, 2014Co-Authors: Olivier Piguet, Michael Hornberger, Muireann Irish, John R. HodgesAbstract:Conflicting evidence exists regarding the integrity of episodic memory in the behavioral variant of frontotemporal Dementia (bvFTD). Recent converging evidence suggests that episodic memory in progressive cases of bvFTD is compromised to the same extent as in Alzheimer's disease (AD). The underlying neural substrates of these episodic memory deficits, however, likely differ contingent on Dementia type. In this study we sought to elucidate the neural substrates of episodic memory performance, across recall and recognition tasks, in both patient groups using voxel-based morphometry (VBM) analyses. We predicted that episodic memory dysfunction would be apparent in both patient groups but would relate to divergent patterns of neural atrophy specific to each Dementia type. We assessed episodic memory, across verbal and visual domains, in 19 bvFTD, 18 AD patients, and 19 age- and education-matched controls. Behaviorally, patient groups were indistinguishable for immediate and delayed recall, across verbal and visual domains. Whole-brain VBM analyses revealed regions commonly implicated in episodic retrieval across groups, namely the right temporal pole, right frontal lobe, left paracingulate gyrus, and right anterior hippocampus. Divergent neural networks specific to each group were also identified. Whereas a widespread network including posterior regions such as the posterior cingulate cortex, parietal and occipital cortices was exclusively implicated in AD, the frontal and anterior temporal lobes underpinned the episodic memory deficits in bvFTD. Our results point to distinct neural changes underlying episodic memory decline specific to each Dementia Syndrome.
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episodic memory in frontotemporal Dementia a critical review
Brain, 2012Co-Authors: Olivier Piguet, Michael HornbergerAbstract:This review offers a critical appraisal of the literature on episodic memory performance in frontotemporal Dementia. Historically, description of patients diagnosed with what was then known as Pick's disease included the presence of memory deficits and an underlying amnestic Syndrome was noted in some of these patients. Over the last 20 years, however, the clinical view has been that episodic memory processing is relatively intact in the frontotemporal Dementia Syndrome. In particular, patients with the subtypes of behavioural variant frontotemporal Dementia and progressive non-fluent aphasia are reported to perform within normal limits on standard memory tests. In the third clinical presentation of frontotemporal Dementia, semantic Dementia, relatively intact episodic memory against a significantly impaired semantic memory was regarded as the hallmark. This position was instrumental in the development of clinical diagnostic criteria for frontotemporal Dementia in which amnesia was explicitly listed as an exclusion criterion for the disease. The relative intactness of episodic memory, therefore, appeared to be a useful diagnostic marker to distinguish early frontotemporal Dementia from Alzheimer's disease, in which early episodic memory disturbance remains the most common clinical feature. We argue that recent evidence questions the validity of preserved episodic memory in frontotemporal Dementia, particularly in behavioural variant frontotemporal Dementia. In semantic Dementia, a complex picture emerges with preservation of some components of episodic memory, notably recognition-based visual memory and recall of recent autobiographical events. We propose a critical synthesis of recent neuropsychological evidence on retrograde and anterograde memory in light of neuroimaging and neuropathological findings, demonstrating involvement of medial temporal structures in frontotemporal Dementia, structures known to be critical for episodic memory processing. We further argue that the multifactorial nature of most memory tests commonly used clinically fail to capture the memory deficits in frontotemporal Dementia and that sensitive assessment tools of memory are needed. Together, recent clinical and experimental findings and the historical evidence represent a strong case for a re-evaluation of the importance of memory disturbance in the clinical diagnosis of frontotemporal Dementia. * Abbreviations : FTD : frontotemporal Dementia PNFA : progressive non-fluent aphasia
Emil M. Hansson - One of the best experts on this subject based on the ideXlab platform.
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notch signaling regulates platelet derived growth factor receptor β expression in vascular smooth muscle cells
Circulation Research, 2008Co-Authors: Shaobo Jin, Emil M. Hansson, Saara Tikka, Fredrik Lanner, Cecilia Sahlgren, Filip Farnebo, Marc Baumann, Hannu Kalimo, Urban LendahlAbstract:Notch signaling is critically important for proper architecture of the vascular system, and mutations in NOTCH3 are associated with CADASIL, a stroke and Dementia Syndrome with vascular smooth muscle cell (VSMC) dysfunction. In this report, we link Notch signaling to platelet-derived growth factor (PDGF) signaling, a key determinant of VSMC biology, and show that PDGF receptor (PDGFR)-beta is a novel immediate Notch target gene. PDGFR-beta expression was upregulated by Notch ligand induction or by activated forms of the Notch receptor. Moreover, upregulation of PDGFR-beta expression in response to Notch activation critically required the Notch signal integrator CSL. In primary VSMCs, PDGFR-beta expression was robustly upregulated by Notch signaling, leading to an augmented intracellular response to PDGF stimulation. In newborn Notch3-deficient mice, PDGFR-beta expression was strongly reduced in the VSMCs that later develop an aberrant morphology. In keeping with this, PDGFR-beta upregulation in response to Notch activation was reduced also in Notch3-deficient embryonic stem cells. Finally, in VSMCs from a CADASIL patient carrying a NOTCH3 missense mutation, upregulation of PDGFR-beta mRNA and protein in response to ligand-induced Notch activation was significantly reduced. In sum, these data reveal a hierarchy for 2 important signaling systems, Notch and PDGF, in the vasculature and provide insights into how dysregulated Notch signaling perturbs VSMC differentiation and function.
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notch signaling regulates platelet derived growth factor receptor β expression in vascular smooth muscle cells
Circulation Research, 2008Co-Authors: Emil M. Hansson, Saara Tikka, Fredrik Lanner, Cecilia Sahlgren, Filip Farnebo, Marc Baumann, Hannu Kalimo, Urban LendahlAbstract:Notch signaling is critically important for proper architecture of the vascular system, and mutations in NOTCH3 are associated with CADASIL, a stroke and Dementia Syndrome with vascular smooth muscle cell (VSMC) dysfunction. In this report, we link Notch signaling to platelet-derived growth factor (PDGF) signaling, a key determinant of VSMC biology, and show that PDGF receptor ( PDGFR )-β is a novel immediate Notch target gene. PDGFR -β expression was upregulated by Notch ligand induction or by activated forms of the Notch receptor. Moreover, upregulation of PDGFR -β expression in response to Notch activation critically required the Notch signal integrator CSL. In primary VSMCs, PDGFR -β expression was robustly upregulated by Notch signaling, leading to an augmented intracellular response to PDGF stimulation. In newborn Notch3 -deficient mice, PDGFR-β expression was strongly reduced in the VSMCs that later develop an aberrant morphology. In keeping with this, PDGFR-β upregulation in response to Notch activation was reduced also in Notch3 -deficient embryonic stem cells. Finally, in VSMCs from a CADASIL patient carrying a NOTCH3 missense mutation, upregulation of PDGFR -β mRNA and protein in response to ligand-induced Notch activation was significantly reduced. In sum, these data reveal a hierarchy for 2 important signaling systems, Notch and PDGF, in the vasculature and provide insights into how dysregulated Notch signaling perturbs VSMC differentiation and function.
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Mouse Notch 3 expression in the pre- and postnatal brain: relationship to the stroke and Dementia Syndrome CADASIL.
Experimental cell research, 2002Co-Authors: Nilima Prakash, Emil M. Hansson, Christer Betsholtz, Thimios A. Mitsiadis, Urban LendahlAbstract:Mutations in the human Notch 3 gene cause the vascular stroke and Dementia Syndrome CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) characterized by degeneration of vascular smooth muscle cells and multiple small infarcts in the white and deep gray matter of the brain. Here we have analyzed the expression pattern of the Notch 3 gene in the pre- and postnatal mouse brain. Prenatal Notch 3 expression is restricted to a scattered population of cells within the vessel wall of all major blood vessels in the developing embryo, including those that form the perineural vascular plexus. Expression in the postnatal brain is confined to a scattered cell population within the vessel wall of small to medium-sized penetrating arteries, which are the vessel type primarily affected in CADASIL patients. In contrast, no expression was observed in capillaries and veins. Notch 3 is most likely expressed in a subset of vascular smooth muscle cells, and the expression pattern of one of the Notch ligands, Serrate 1, was very similar to that observed for Notch 3. The Notch 3 expressing pattern was not significantly altered in platelet-derived growth factor B- (PDGF-B) deficient mouse embryos, demonstrating that Notch 3 expression is not under direct control of PDGF-B. These data show that Notch 3 expression is conserved between mouse and human and suggest that the mouse is a valid system for analysis of CADASIL.
Olivier Piguet - One of the best experts on this subject based on the ideXlab platform.
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common and unique gray matter correlates of episodic memory dysfunction in frontotemporal Dementia and alzheimer s disease
Human Brain Mapping, 2014Co-Authors: Olivier Piguet, Michael Hornberger, Muireann Irish, John R. HodgesAbstract:Conflicting evidence exists regarding the integrity of episodic memory in the behavioral variant of frontotemporal Dementia (bvFTD). Recent converging evidence suggests that episodic memory in progressive cases of bvFTD is compromised to the same extent as in Alzheimer's disease (AD). The underlying neural substrates of these episodic memory deficits, however, likely differ contingent on Dementia type. In this study we sought to elucidate the neural substrates of episodic memory performance, across recall and recognition tasks, in both patient groups using voxel-based morphometry (VBM) analyses. We predicted that episodic memory dysfunction would be apparent in both patient groups but would relate to divergent patterns of neural atrophy specific to each Dementia type. We assessed episodic memory, across verbal and visual domains, in 19 bvFTD, 18 AD patients, and 19 age- and education-matched controls. Behaviorally, patient groups were indistinguishable for immediate and delayed recall, across verbal and visual domains. Whole-brain VBM analyses revealed regions commonly implicated in episodic retrieval across groups, namely the right temporal pole, right frontal lobe, left paracingulate gyrus, and right anterior hippocampus. Divergent neural networks specific to each group were also identified. Whereas a widespread network including posterior regions such as the posterior cingulate cortex, parietal and occipital cortices was exclusively implicated in AD, the frontal and anterior temporal lobes underpinned the episodic memory deficits in bvFTD. Our results point to distinct neural changes underlying episodic memory decline specific to each Dementia Syndrome.
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episodic memory in frontotemporal Dementia a critical review
Brain, 2012Co-Authors: Olivier Piguet, Michael HornbergerAbstract:This review offers a critical appraisal of the literature on episodic memory performance in frontotemporal Dementia. Historically, description of patients diagnosed with what was then known as Pick's disease included the presence of memory deficits and an underlying amnestic Syndrome was noted in some of these patients. Over the last 20 years, however, the clinical view has been that episodic memory processing is relatively intact in the frontotemporal Dementia Syndrome. In particular, patients with the subtypes of behavioural variant frontotemporal Dementia and progressive non-fluent aphasia are reported to perform within normal limits on standard memory tests. In the third clinical presentation of frontotemporal Dementia, semantic Dementia, relatively intact episodic memory against a significantly impaired semantic memory was regarded as the hallmark. This position was instrumental in the development of clinical diagnostic criteria for frontotemporal Dementia in which amnesia was explicitly listed as an exclusion criterion for the disease. The relative intactness of episodic memory, therefore, appeared to be a useful diagnostic marker to distinguish early frontotemporal Dementia from Alzheimer's disease, in which early episodic memory disturbance remains the most common clinical feature. We argue that recent evidence questions the validity of preserved episodic memory in frontotemporal Dementia, particularly in behavioural variant frontotemporal Dementia. In semantic Dementia, a complex picture emerges with preservation of some components of episodic memory, notably recognition-based visual memory and recall of recent autobiographical events. We propose a critical synthesis of recent neuropsychological evidence on retrograde and anterograde memory in light of neuroimaging and neuropathological findings, demonstrating involvement of medial temporal structures in frontotemporal Dementia, structures known to be critical for episodic memory processing. We further argue that the multifactorial nature of most memory tests commonly used clinically fail to capture the memory deficits in frontotemporal Dementia and that sensitive assessment tools of memory are needed. Together, recent clinical and experimental findings and the historical evidence represent a strong case for a re-evaluation of the importance of memory disturbance in the clinical diagnosis of frontotemporal Dementia. * Abbreviations : FTD : frontotemporal Dementia PNFA : progressive non-fluent aphasia
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piano playing skills in a patient with frontotemporal Dementia a longitudinal case study
Proceedings of the International Symposium on Performance Science, 2009Co-Authors: Sharpley Hsieh, Olivier Piguet, Eneida Mioshi, Felicity A Baker, John R. HodgesAbstract:Patients with Dementia, such as Alzheimer’s disease, can continue to play the piano skillfully despite profound cognitive impairment. It has been suggested that this may be because these skills have been well-rehearsed and become automatic motor movements. Less is known about how these musical skills may be related to the performance of everyday functional abilities and, also, how the ability to play a musical instrument may be affected in other Dementia types. Recordings of a patient diagnosed with behavioral-variant frontotemporal Dementia, a Dementia Syndrome clinically characterized by marked behavioral and cognitive changes, playing the piano was taken 12 months apart. Aspects of musical performance (accuracy, tone quality, dynamics, rhythm, tempo, and interpretation) were rated by professional musical teachers. The physical and mental skills required to complete activities of daily living were assessed. Tests of cognitive functioning and brain imaging were also conducted over this period. Results showed that over one year, significant declines were observed in the areas of cognition, the mental abilities required for everyday skills, as well as brain atrophy on imaging. Physical skills for the performance of activities of daily living were relatively preserved, as was the ability to play the piano. These findings confirm previous reports and demonstrate the relative independence of procedural skills in the context of significant cognitive impairment in patients with Dementia.
Saara Tikka - One of the best experts on this subject based on the ideXlab platform.
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notch signaling regulates platelet derived growth factor receptor β expression in vascular smooth muscle cells
Circulation Research, 2008Co-Authors: Emil M. Hansson, Saara Tikka, Fredrik Lanner, Cecilia Sahlgren, Filip Farnebo, Marc Baumann, Hannu Kalimo, Urban LendahlAbstract:Notch signaling is critically important for proper architecture of the vascular system, and mutations in NOTCH3 are associated with CADASIL, a stroke and Dementia Syndrome with vascular smooth muscle cell (VSMC) dysfunction. In this report, we link Notch signaling to platelet-derived growth factor (PDGF) signaling, a key determinant of VSMC biology, and show that PDGF receptor ( PDGFR )-β is a novel immediate Notch target gene. PDGFR -β expression was upregulated by Notch ligand induction or by activated forms of the Notch receptor. Moreover, upregulation of PDGFR -β expression in response to Notch activation critically required the Notch signal integrator CSL. In primary VSMCs, PDGFR -β expression was robustly upregulated by Notch signaling, leading to an augmented intracellular response to PDGF stimulation. In newborn Notch3 -deficient mice, PDGFR-β expression was strongly reduced in the VSMCs that later develop an aberrant morphology. In keeping with this, PDGFR-β upregulation in response to Notch activation was reduced also in Notch3 -deficient embryonic stem cells. Finally, in VSMCs from a CADASIL patient carrying a NOTCH3 missense mutation, upregulation of PDGFR -β mRNA and protein in response to ligand-induced Notch activation was significantly reduced. In sum, these data reveal a hierarchy for 2 important signaling systems, Notch and PDGF, in the vasculature and provide insights into how dysregulated Notch signaling perturbs VSMC differentiation and function.
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notch signaling regulates platelet derived growth factor receptor β expression in vascular smooth muscle cells
Circulation Research, 2008Co-Authors: Shaobo Jin, Emil M. Hansson, Saara Tikka, Fredrik Lanner, Cecilia Sahlgren, Filip Farnebo, Marc Baumann, Hannu Kalimo, Urban LendahlAbstract:Notch signaling is critically important for proper architecture of the vascular system, and mutations in NOTCH3 are associated with CADASIL, a stroke and Dementia Syndrome with vascular smooth muscle cell (VSMC) dysfunction. In this report, we link Notch signaling to platelet-derived growth factor (PDGF) signaling, a key determinant of VSMC biology, and show that PDGF receptor (PDGFR)-beta is a novel immediate Notch target gene. PDGFR-beta expression was upregulated by Notch ligand induction or by activated forms of the Notch receptor. Moreover, upregulation of PDGFR-beta expression in response to Notch activation critically required the Notch signal integrator CSL. In primary VSMCs, PDGFR-beta expression was robustly upregulated by Notch signaling, leading to an augmented intracellular response to PDGF stimulation. In newborn Notch3-deficient mice, PDGFR-beta expression was strongly reduced in the VSMCs that later develop an aberrant morphology. In keeping with this, PDGFR-beta upregulation in response to Notch activation was reduced also in Notch3-deficient embryonic stem cells. Finally, in VSMCs from a CADASIL patient carrying a NOTCH3 missense mutation, upregulation of PDGFR-beta mRNA and protein in response to ligand-induced Notch activation was significantly reduced. In sum, these data reveal a hierarchy for 2 important signaling systems, Notch and PDGF, in the vasculature and provide insights into how dysregulated Notch signaling perturbs VSMC differentiation and function.