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Full-Text Articles in Physiological Processes

Potential Targeting Mechanisms For Bone-Directed Therapies, Betul Celik, Andrés Leal, Shunji Tomatsu Jul 2024

Potential Targeting Mechanisms For Bone-Directed Therapies, Betul Celik, Andrés Leal, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Bone development is characterized by complex regulation mechanisms, including signal transduction and transcription factor-related pathways, glycobiological processes, cellular interactions, transportation mechanisms, and, importantly, chemical formation resulting from hydroxyapatite. Any abnormal regulation in the bone development processes causes skeletal system-related problems. To some extent, the avascularity of cartilage and bone makes drug delivery more challenging than that of soft tissues. Recent studies have implemented many novel bone-targeting approaches to overcome drawbacks. However, none of these strategies fully corrects skeletal dysfunction, particularly in growth plate-related ones. Although direct recombinant enzymes (e.g., Vimizim for Morquio, Cerezyme for Gaucher, Elaprase for Hunter, Mepsevii for …

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Persistent Stress-Induced Neuroplastic Changes In The Locus Coeruleus/Norepinephrine System, Olga Borodovitsyna, Neal Joshi, Daniel Chandler Jan 2018

Persistent Stress-Induced Neuroplastic Changes In The Locus Coeruleus/Norepinephrine System, Olga Borodovitsyna, Neal Joshi, Daniel Chandler

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Neural plasticity plays a critical role in mediating short- and long-term brain responses to environmental stimuli. A major effector of plasticity throughout many regions of the brain is stress. Activation of the locus coeruleus (LC) is a critical step in mediating the neuroendocrine and behavioral limbs of the stress response. During stressor exposure, activation of the hypothalamic-pituitary-adrenal axis promotes release of corticotropin-releasing factor in LC, where its signaling promotes a number of physiological and cellular changes. While the acute effects of stress on LC physiology have been described, its long-term effects are less clear. This review will describe how stress …

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Local Corticotropin Releasing Hormone (Crh) Signals To Its Receptor Crhr1 During Postnatal Development Of The Mouse Olfactory Bulb, Isabella Garcia, Paramjit K Bhullar, Burak Tepe, Joshua Ortiz-Guzman, Longwen Huang, Alexander M Herman, Lesley Chaboub, Benjamin Deneen, Nicholas J Justice, Benjamin R Arenkiel Jan 2016

Local Corticotropin Releasing Hormone (Crh) Signals To Its Receptor Crhr1 During Postnatal Development Of The Mouse Olfactory Bulb, Isabella Garcia, Paramjit K Bhullar, Burak Tepe, Joshua Ortiz-Guzman, Longwen Huang, Alexander M Herman, Lesley Chaboub, Benjamin Deneen, Nicholas J Justice, Benjamin R Arenkiel

Faculty, Staff and Students Publications

Neuropeptides play important physiological functions during distinct behaviors such as arousal, learning, memory, and reproduction. However, the role of local, extrahypothalamic neuropeptide signaling in shaping synapse formation and neuronal plasticity in the brain is not well understood. Here, we characterize the spatiotemporal expression profile of the neuropeptide corticotropin-releasing hormone (CRH) and its receptor CRHR1 in the mouse OB throughout development. We found that CRH-expressing interneurons are present in the external plexiform layer, that its cognate receptor is expressed by granule cells, and show that both CRH and CRHR1 expression enriches in the postnatal period when olfaction becomes important towards olfactory-related …

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Syndecan 4 Is Required For Endothelial Alignment In Flow And Atheroprotective Signaling, Nicolas Baeyens, Mary Jo Mulligan-Kehoe, Federico Corti, David D. Simon, Tyler D. Ross, John M. Rhodes, Thomas Z. Wang Dec 2014

Syndecan 4 Is Required For Endothelial Alignment In Flow And Atheroprotective Signaling, Nicolas Baeyens, Mary Jo Mulligan-Kehoe, Federico Corti, David D. Simon, Tyler D. Ross, John M. Rhodes, Thomas Z. Wang

Dartmouth Scholarship

Atherosclerotic plaque localization correlates with regions of disturbed flow in which endothelial cells (ECs) align poorly, whereas sustained laminar flow correlates with cell alignment in the direction of flow and resistance to atherosclerosis. We now report that in hypercholesterolemic mice, deletion of syndecan 4 (S4−/−) drastically increased atherosclerotic plaque burden with the appearance of plaque in normally resistant locations. Strikingly, ECs from the thoracic aortas of S4−/− mice were poorly aligned in the direction of the flow. Depletion of S4 in human umbilical vein endothelial cells (HUVECs) using shRNA also inhibited flow-induced alignment in vitro, which was rescued by re-expression …

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Endothelial-Specific Expression Of Caveolin-1 Impairs Microvascular Permeability And Angiogenesis, Philip M. Bauer, Jun Yu, Yan Chen, Reed Hickey, Pascal N. Bernatchez, Robin Looft-Wilson, Yan Huang, Frank Giordano, Radu V. Stan, William C. Sessa Jan 2005

Endothelial-Specific Expression Of Caveolin-1 Impairs Microvascular Permeability And Angiogenesis, Philip M. Bauer, Jun Yu, Yan Chen, Reed Hickey, Pascal N. Bernatchez, Robin Looft-Wilson, Yan Huang, Frank Giordano, Radu V. Stan, William C. Sessa

Dartmouth Scholarship

The functions of caveolae and/or caveolins in intact animals are beginning to be explored. Here, by using endothelial cell-specific transgenesis of the caveolin-1 (Cav-1) gene in mice, we show the critical role of Cav-1 in several postnatal vascular paradigms. First, increasing levels of Cav-1 do not increase caveolae number in the endothelium in vivo. Second, despite a lack of quantitative changes in organelle number, endothelial-specific expression of Cav-1 impairs endothelial nitric oxide synthase activation, endothelial barrier function, and angiogenic responses to exogenous VEGF and tissue ischemia. In addition, VEGF-mediated phosphorylation of Akt and its substrate, endothelial nitric oxide synthase, were …

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Aldosterone Stimulates K Secretion Across Mammalian Colon Independent Of Na Absorption, Gerhard Rechkemmer, Dan R. Halm Jan 1989

Aldosterone Stimulates K Secretion Across Mammalian Colon Independent Of Na Absorption, Gerhard Rechkemmer, Dan R. Halm

Neuroscience, Cell Biology & Physiology Faculty Publications

K transport across guinea pig (Cavia porcellus) distal colon was measured in vitro using isotopically determined unidirectional fluxes. Aldosterone stimulated electrogenic Na absorption, as measured by amiloride-sensitive short-circuit current (Isc), and reduced net K absorption from +2.5 ± 0.2 µEq/cm2 per hr to +0.8 ± 0.3 µEq/cm2 per hr (mean ± SEM). Amiloride addition to the mucosal solution did not enhance net K absorption, as expected if inhibiting active Na absorption would reduce active K secretion as in the distal nephron. The amiloride-insensitive Isc was -1.0 ± 0.2 µEq/cm2 per hr (mean ± SEM) …

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