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Full-Text Articles in Cell and Developmental Biology

An Analysis Of The Myocardial Transcriptome In A Mouse Model Of Cardiac Dysfunction With Decreased Cholinergic Neurotransmission, Ashbeel Roy, Aline Lara, Diogo Guimaraes, Rita Pires, Eneas R. Gomes, David E. Carter, Marcus V. Gomez, Silvia Guatimosim, Vania F. Prado, Marco A. M. Prado, Robert Gros Jun 2012

An Analysis Of The Myocardial Transcriptome In A Mouse Model Of Cardiac Dysfunction With Decreased Cholinergic Neurotransmission, Ashbeel Roy, Aline Lara, Diogo Guimaraes, Rita Pires, Eneas R. Gomes, David E. Carter, Marcus V. Gomez, Silvia Guatimosim, Vania F. Prado, Marco A. M. Prado, Robert Gros

Anatomy and Cell Biology Publications

Autonomic dysfunction is observed in many cardiovascular diseases and contributes to cardiac remodeling and heart disease. We previously reported that a decrease in the expression levels of the vesicular acetylcholine transporter (VAChT) in genetically-modified homozygous mice (VAChT KDHOM) leads to decreased cholinergic tone, autonomic imbalance and a phenotype resembling cardiac dysfunction. In order to further understand the molecular changes resulting from chronic long-term decrease in parasympathetic tone, we undertook a transcriptome-based, microarray-driven approach to analyze gene expression changes in ventricular tissue from VAChT KDHOM mice. We demonstrate that a decrease in cholinergic tone is associated with alterations in gene expression …


Natural Reward Experience Alters Ampa And Nmda Receptor Distribution And Function In The Nucleus Accumbens, Kyle K. Pitchers, Susanne Schmid, Andrea R. Di Sebastiano, Xu Wang, Steven R. Laviolette, Michael N. Lehman, Lique M. Coolen Apr 2012

Natural Reward Experience Alters Ampa And Nmda Receptor Distribution And Function In The Nucleus Accumbens, Kyle K. Pitchers, Susanne Schmid, Andrea R. Di Sebastiano, Xu Wang, Steven R. Laviolette, Michael N. Lehman, Lique M. Coolen

Anatomy and Cell Biology Publications

Natural reward and drugs of abuse converge upon the mesolimbic system which mediates motivation and reward behaviors. Drugs induce neural adaptations in this system, including transcriptional, morphological, and synaptic changes, which contribute to the development and expression of drug-related memories and addiction. Previously, it has been reported that sexual experience in male rats, a natural reward behavior, induces similar neuroplasticity in the mesolimbic system and affects natural reward and drug-related behavior. The current study determined whether sexual experience causes long-lasting changes in mating, or ionotropic glutamate receptor trafficking or function in the nucleus accumbens (NAc), following 3 different reward abstinence …


Perceptual Enhancement Of Arteriovenous Malformation In Mri Angiography Displays, Abhari Kamyar, John S. H. Baxter, Roy Eagleson, Terry Peters, Sandrine De Ribaupierre Jan 2012

Perceptual Enhancement Of Arteriovenous Malformation In Mri Angiography Displays, Abhari Kamyar, John S. H. Baxter, Roy Eagleson, Terry Peters, Sandrine De Ribaupierre

Anatomy and Cell Biology Publications

The importance of presenting medical images in an intuitive and usable manner during a procedure is essential. However, most medical visualization interfaces, particularly those designed for minimally-invasive surgery, suffer from a number of issues as a consequence of disregarding the human perceptual, cognitive, and motor system's limitations. This matter is even more prominent when human visual system is overlooked during the design cycle. One example is the visualization of the neuro-vascular structures in MR angiography (MRA) images. This study investigates perceptual performance in the usability of a display to visualize blood vessels in MRA volumes using a contour enhancement technique. …


Dha Supplemented In Peptamen Diet Offers No Advantage In Pathways To Amyloidosis: Is It Time To Evaluate Composite Lipid Diet?, Zareen Amtul, Mary Keet, Peter Merrifield, David Westaway, Richard F. Rozmahel Sep 2011

Dha Supplemented In Peptamen Diet Offers No Advantage In Pathways To Amyloidosis: Is It Time To Evaluate Composite Lipid Diet?, Zareen Amtul, Mary Keet, Peter Merrifield, David Westaway, Richard F. Rozmahel

Anatomy and Cell Biology Publications

Numerous reports have documented the beneficial effects of dietary docosahexaenoic acid (DHA) on beta-amyloid production and Alzheimer's disease (AD). However, none of these studies have examined and compared DHA, in combination with other dietary nutrients, for its effects on plaque pathogenesis. Potential interactions of DHA with other dietary nutrients and fatty acids are conventionally ignored. Here we investigated DHA with two dietary regimes; peptamen (pep+DHA) and low fat diet (low fat+DHA). Peptamen base liquid diet is a standard sole-source nutrition for patients with gastrointestinal dysfunction. Here we demonstrate that a robust AD transgenic mouse model shows an increased tendency to …


Habituation And Prepulse Inhibition Of The Acoustic Startle In Rodents, Bridget Valsamis, Susanne Schmid Sep 2011

Habituation And Prepulse Inhibition Of The Acoustic Startle In Rodents, Bridget Valsamis, Susanne Schmid

Anatomy and Cell Biology Publications

The acoustic startle response is a protective response, elicited by a sudden and intense acoustic stimulus. Facial and skeletal muscles are activated within a few milliseconds, leading to a whole body flinch in rodents. Although startle responses are reflexive responses that can be reliably elicited, they are not stereotypic. They can be modulated by emotions such as fear (fear potentiated startle) and joy (joy attenuated startle), by non-associative learning processes such as habituation and sensitization, and by other sensory stimuli through sensory gating processes (prepulse inhibition), turning startle responses into an excellent tool for assessing emotions, learning, and sensory gating. …


Imaging Mass Spectrometry Detection Of Gangliosides Species Within The Mouse Brain Following Transient Focal Cerebral Ischemia, Shawn N. Whitehead, Kenneth H. N. Chan, Sandhya Gangaraju, Jacqueline Slinn, Jianjun Li, Sheng T. Hou Jun 2011

Imaging Mass Spectrometry Detection Of Gangliosides Species Within The Mouse Brain Following Transient Focal Cerebral Ischemia, Shawn N. Whitehead, Kenneth H. N. Chan, Sandhya Gangaraju, Jacqueline Slinn, Jianjun Li, Sheng T. Hou

Anatomy and Cell Biology Publications

Gangliosides, a member of the glycosphingolipid family, are heterogeneously expressed in biological membranes and are particularly enriched within the central nervous system. Gangliosides consist of mono- or poly-sialylated oligosaccharide chains of variable lengths attached to a ceramide unit and are found to be intimately involved in brain disease development. The purpose of this study is to examine the spatial profile of ganglioside species using matrix-assisted laser desorption/ionization (MALDI) imaging (IMS) following middle cerebral artery occlusion (MCAO) reperfusion injury in the mouse. IMS is a powerful method to not only discriminate gangliosides by their oligosaccharide components, but also by their carbon …


Vacht Knock-Down Mice Show Normal Prepulse Inhibition But Disrupted Long-Term Habituation, S. Schmid, E. Azzopardi, X. De Jaeger, Marco Prado, V. F. Prado Jun 2011

Vacht Knock-Down Mice Show Normal Prepulse Inhibition But Disrupted Long-Term Habituation, S. Schmid, E. Azzopardi, X. De Jaeger, Marco Prado, V. F. Prado

Anatomy and Cell Biology Publications

The neurotransmitter acetylcholine (ACh) plays a crucial role in both the central and peripheral nervous system. Central cholinergic transmission is important for cognitive functions and cholinergic disruptions have been associated with different neural disorders. We here tested the role of cholinergic transmission in basic cognitive functions, i.e. in prepulse inhibition (PPI) and short-term habituation (STH) as well as long-term habituation (LTH) of startle using mice with a 65% knockdown (KD) of the vesicular ACh transporter (VAChT). These mice are slow in refilling cholinergic synaptic transmitter vesicles, leading to a reduced cholinergic tone. Prepulse inhibition has been assumed to be mediated …


Ocular Pathology Relevant To Glaucoma In A Gja1(Jrt) Mouse Model Of Human Oculodentodigital Dysplasia, Edmund Tsui, Kathleen A. Hill, Alex M. Laliberte, Daniel Paluzzi, Ilia Kisilevksy, Qing Shao, Godfrey J. Heathcote, Dale W. Laird, Gerald M. Kidder, Cindy M. L. Hutnik May 2011

Ocular Pathology Relevant To Glaucoma In A Gja1(Jrt) Mouse Model Of Human Oculodentodigital Dysplasia, Edmund Tsui, Kathleen A. Hill, Alex M. Laliberte, Daniel Paluzzi, Ilia Kisilevksy, Qing Shao, Godfrey J. Heathcote, Dale W. Laird, Gerald M. Kidder, Cindy M. L. Hutnik

Anatomy and Cell Biology Publications

PURPOSE. Oculodentodigital dysplasia (ODDD) is a human disorder caused by mutations in the gap junction alpha 1 (GJA1) gene encoding the connexin43 (Cx43) gap junction protein. Causal links between GJA1 mutations and glaucoma are not understood. The purpose in this study was to examine the ocular phenotype for Gja1(Jrt/+) mice harboring a Cx43 G60S mutation. METHODS. In young Gja1(Jrt/+) mice, Cx43 abundance was assessed with a Western blot, and Cx43 localization was visualized using immunohistochemistry and confocal microscopy. Intraocular pressure (IOP) was measured by rebound tonometry, and eye anatomy was imaged using ocular coherence tomography (OCT). Hematoxylin and eosin (H&E)-stained …


Novel Strains Of Mice Deficient For The Vesicular Acetylcholine Transporter: Insights On Transcriptional Regulation And Control Of Locomotor Behavior, Christina Martins-Silva, Xavier De Jaeger, Monica S. Guzman, Ricardo D. F. Lima, Magda S. Santos, Christopher Kushmerick, Marcus V. Gomez, Marc G. Caron, Marco A. M. Prado, Vania F. Prado Mar 2011

Novel Strains Of Mice Deficient For The Vesicular Acetylcholine Transporter: Insights On Transcriptional Regulation And Control Of Locomotor Behavior, Christina Martins-Silva, Xavier De Jaeger, Monica S. Guzman, Ricardo D. F. Lima, Magda S. Santos, Christopher Kushmerick, Marcus V. Gomez, Marc G. Caron, Marco A. M. Prado, Vania F. Prado

Anatomy and Cell Biology Publications

Defining the contribution of acetylcholine to specific behaviors has been challenging, mainly because of the difficulty in generating suitable animal models of cholinergic dysfunction. We have recently shown that, by targeting the vesicular acetylcholine transporter (VAChT) gene, it is possible to generate genetically modified mice with cholinergic deficiency. Here we describe novel VAChT mutant lines. VAChT gene is embedded within the first intron of the choline acetyltransferase (ChAT) gene, which provides a unique arrangement and regulation for these two genes. We generated a VAChT allele that is flanked by loxP sequences and carries the resistance cassette placed in a ChAT …


Role Of Alpha 7 Nicotinic Acetylcholine Receptor In Calcium Signaling Induced By Prion Protein Interaction With Stress-Inducible Protein 1, Flavio H. Beraldo, Camila P. Arantes, Tiago G. Santos, Nicolle G. T. Queiroz, Kirk Young, Jane R. Rylett, Regina P. Markus, Marco A. M. Prado, Vilma R. Martins Nov 2010

Role Of Alpha 7 Nicotinic Acetylcholine Receptor In Calcium Signaling Induced By Prion Protein Interaction With Stress-Inducible Protein 1, Flavio H. Beraldo, Camila P. Arantes, Tiago G. Santos, Nicolle G. T. Queiroz, Kirk Young, Jane R. Rylett, Regina P. Markus, Marco A. M. Prado, Vilma R. Martins

Anatomy and Cell Biology Publications

The prion protein (PrP(C)) is a conserved glycosylphosphatidyl-inositol-anchored cell surface protein expressed by neurons and other cells. Stress-inducible protein 1 (STI1) binds PrP(C) extracellularly, and this activated signaling complex promotes neuronal differentiation and neuroprotection via the extracellular signal-regulated kinase 1 and 2 (ERK1/2) and cAMP-dependent protein kinase 1 (PKA) pathways. However, the mechanism by which the PrPC-STI1 interaction transduces extracellular signals to the intracellular environment is unknown. We found that in hippocampal neurons, STI1-PrP(C) engagement induces an increase in intracellular Ca(2+) levels. This effect was not detected in PrP(C)-null neurons or wild-type neurons treated with an STI1 mutant unable to …


Dysautonomia Due To Reduced Cholinergic Neurotransmission Causes Cardiac Remodeling And Heart Failure, Aline Lara, Denis D. Damasceno, Rita Pires, Robert Gros, Eneas R. Gomes, Mariana Gavioli, Ricardo F. Lima, Diogo Guimaraes, Patricia Lima, Carlos Roberto Bueno Jr., Anilton Vasconcelos, Danilo Roman-Campos, Cristiane A. S. Menezes, Raquel A. Sirvente, Vera M. Salemi, Charles Mady, Marc G. Caron, Anderson J. Ferreira, Patricia C. Brum, Rodrigo R. Resende, Jader S. Cruz, Marcus Vinicius Gomez, Vania F. Prado, Alvair P. De Almeida, Marco A. M. Prado, Silvia Guatimosim Apr 2010

Dysautonomia Due To Reduced Cholinergic Neurotransmission Causes Cardiac Remodeling And Heart Failure, Aline Lara, Denis D. Damasceno, Rita Pires, Robert Gros, Eneas R. Gomes, Mariana Gavioli, Ricardo F. Lima, Diogo Guimaraes, Patricia Lima, Carlos Roberto Bueno Jr., Anilton Vasconcelos, Danilo Roman-Campos, Cristiane A. S. Menezes, Raquel A. Sirvente, Vera M. Salemi, Charles Mady, Marc G. Caron, Anderson J. Ferreira, Patricia C. Brum, Rodrigo R. Resende, Jader S. Cruz, Marcus Vinicius Gomez, Vania F. Prado, Alvair P. De Almeida, Marco A. M. Prado, Silvia Guatimosim

Anatomy and Cell Biology Publications

Overwhelming evidence supports the importance of the sympathetic nervous system in heart failure. In contrast, much less is known about the role of failing cholinergic neurotransmission in cardiac disease. By using a unique genetically modified mouse line with reduced expression of the vesicular acetylcholine transporter (VAChT) and consequently decreased release of acetylcholine, we investigated the consequences of altered cholinergic tone for cardiac function. M-mode echocardiography, hemodynamic experiments, analysis of isolated perfused hearts, and measurements of cardiomyocyte contraction indicated that VAChT mutant mice have decreased left ventricle function associated with altered calcium handling. Gene expression was analyzed by quantitative reverse transcriptase …


Neuropilin 1 Directly Interacts With Fer Kinase To Mediate Semaphorin3a-Induced Death Of Cortical Neurons, Susan X. Jiang, Shawn N. Whitehead, Amy Aylsworth, Bogdan Zurakowski, Kenneth Chan, Jianjun Li, Sheng T. Hou Mar 2010

Neuropilin 1 Directly Interacts With Fer Kinase To Mediate Semaphorin3a-Induced Death Of Cortical Neurons, Susan X. Jiang, Shawn N. Whitehead, Amy Aylsworth, Bogdan Zurakowski, Kenneth Chan, Jianjun Li, Sheng T. Hou

Anatomy and Cell Biology Publications

Neuropilins (NRPs) are receptors for the major chemorepulsive axonal guidance cue semaphorins (Sema). The interaction of Sema3A/NRP1 during development leads to the collapse of growth cones. Here we show that Sema3A also induces death of cultured cortical neurons through NRP1. A specific NRP1 inhibitory peptide ameliorated Sema3A-evoked cortical axonal retraction and neuronal death. Moreover, Sema3A was also involved in cerebral ischemia-induced neuronal death. Expression levels of Sema3A and NRP1, but not NRP2, were significantly increased early during brain reperfusion following transient focal cerebral ischemia. NRP1 inhibitory peptide delivered to the ischemic brain was potently neuroprotective and prevented the loss of …


Reduced Expression Of Mir15a In The Blood Of Patients With Oral Squamous Cell Carcinoma Is Associated With Tumor Staging, Joao Artur Ricieri Brito, Carolina Cavalieri Gomes, Flavio Juliano Garcia Santos Pimenta, Alvimar Afonso Barbosa, Marco A. M. Prado, Vania F. Prado, Marcus Vinicius Gomez, Ricardo Santiago Gomez Jan 2010

Reduced Expression Of Mir15a In The Blood Of Patients With Oral Squamous Cell Carcinoma Is Associated With Tumor Staging, Joao Artur Ricieri Brito, Carolina Cavalieri Gomes, Flavio Juliano Garcia Santos Pimenta, Alvimar Afonso Barbosa, Marco A. M. Prado, Vania F. Prado, Marcus Vinicius Gomez, Ricardo Santiago Gomez

Anatomy and Cell Biology Publications

MicroRNAs (miRNAs) mirl 5a and let7a are iMportant regulators of bcl-2, ras and c-myc proteins Considering that these miRNAs are commonly altered in many human cancers and that these proteins are reported to be altered in oral squamous cell carcinoma (OSCC), we investigated them in a set of OSCC cases 'I he miRNAs as well as the proteins were evaluated in the tumor and blood of 20 patients by real-time quantitative PCR and iMmunohistochemistry, respectively The expression of nfirl5a and bcl-2 proteins in the tumors was not associated with each other or with tumor staging On the other hand, we …


The Vesicular Acetylcholine Transporter Is Required For Neuromuscular Development And Function, Braulio M. De Castro, Xavier De Jaeger, Cristina Martins-Silva, Ricardo D. F. Lima, Ernani Amaral, Cristiane Menezes, Patricia Lima, Cintia M. L. Neves, Rita G. Pires, Thomas W. Gould, Ian Welch, Christopher Kushmerick, Cristina Guatimosim, Ivan Izquierdo, Martin Cammarota, Jane R. Rylett, Marcus V. Gomez, Marc G. Caron, Ronald W. Oppenheim, Marco A. M. Prado, Vania F. Prado Oct 2009

The Vesicular Acetylcholine Transporter Is Required For Neuromuscular Development And Function, Braulio M. De Castro, Xavier De Jaeger, Cristina Martins-Silva, Ricardo D. F. Lima, Ernani Amaral, Cristiane Menezes, Patricia Lima, Cintia M. L. Neves, Rita G. Pires, Thomas W. Gould, Ian Welch, Christopher Kushmerick, Cristina Guatimosim, Ivan Izquierdo, Martin Cammarota, Jane R. Rylett, Marcus V. Gomez, Marc G. Caron, Ronald W. Oppenheim, Marco A. M. Prado, Vania F. Prado

Anatomy and Cell Biology Publications

The vesicular acetylcholine (ACh) transporter (VAChT) mediates ACh storage by synaptic vesicles. However, the VAChT-independent release of ACh is believed to be important during development. Here we generated VAChT knockout mice and tested the physiological relevance of the VAChT-independent release of ACh. Homozygous VAChT knockout mice died shortly after birth, indicating that VAChT-mediated storage of ACh is essential for life. Indeed, synaptosomes obtained from brains of homozygous knockouts were incapable of releasing ACh in response to depolarization. Surprisingly, electrophysiological recordings at the skeletal-neuromuscular junction show that VAChT knockout mice present spontaneous miniature end-plate potentials with reduced amplitude and frequency, which …


High Aldehyde Dehydrogenase And Expression Of Cancer Stem Cell Markers Selects For Breast Cancer Cells With Enhanced Malignant And Metastatic Ability, Alysha K. Croker, David Goodale, Jenny Chu, Carl Postenka, Benjamin D. Hedley, David A. Hess, Alison L. Allan Aug 2009

High Aldehyde Dehydrogenase And Expression Of Cancer Stem Cell Markers Selects For Breast Cancer Cells With Enhanced Malignant And Metastatic Ability, Alysha K. Croker, David Goodale, Jenny Chu, Carl Postenka, Benjamin D. Hedley, David A. Hess, Alison L. Allan

Anatomy and Cell Biology Publications

Cancer stem cells (CSCs) have recently been identified in leukaemia and solid tumours; however, the role of CSCs in metastasis remains poorly understood. This dearth of knowledge about CSCs and metastasis is due largely to technical challenges associated with the use of primary human cancer cells in pre-clinical models of metastasis. Therefore, the objective of this study was to develop suitable pre-clinical model systems for studying stem-like cells in breast cancer metastasis, and to test the hypothesis that stem-like cells play a key role in metastatic behaviour. We assessed four different human breast cancer cell lines (MDA-MB-435, MDA-MB-231, MDA-MB-468, MCF-7) …


Erythropoietin Improves Skeletal Muscle Microcirculation And Tissue Bioenergetics In A Mouse Sepsis Model, Raymod Kao, Anargyros Xenocostas, Tao Rui, Weixiong Huang, James Rose, Claudio M. Martin Jan 2007

Erythropoietin Improves Skeletal Muscle Microcirculation And Tissue Bioenergetics In A Mouse Sepsis Model, Raymod Kao, Anargyros Xenocostas, Tao Rui, Weixiong Huang, James Rose, Claudio M. Martin

Anatomy and Cell Biology Publications

Introduction The relationship between oxygen delivery and consumption in sepsis is impaired, suggesting a microcirculatory perfusion defect. Recombinant human erythropoietin ( rHuEPO) regulates erythropoiesis and also exerts complex actions promoting the maintenance of homeostasis of the organism under stress. The objective of this study was to test the hypothesis that rHuEPO could improve skeletal muscle capillary perfusion and tissue oxygenation in sepsis. Methods Septic mice in three experiments received rHu-EPO 400 U/kg subcutaneously 18 hours after cecal ligation and perforation ( CLP). The first experiment measured the acute effects of rHuEPO on hemodynamics, blood counts, and arterial lactate level. The …


Neonatal Brain: Regional Variability Of In Vivo Mr Imaging Relaxation Rates At 3.0 T-Initial Experience, L. A. Williams, N. Gelman, P. A. Picot, D. S. Lee, J. R. Ewing, V. K. Han, R. T. Thompson May 2005

Neonatal Brain: Regional Variability Of In Vivo Mr Imaging Relaxation Rates At 3.0 T-Initial Experience, L. A. Williams, N. Gelman, P. A. Picot, D. S. Lee, J. R. Ewing, V. K. Han, R. T. Thompson

Anatomy and Cell Biology Publications

PURPOSE: To retrospectively investigate regional in vivo magnetic resonance,(MR). imaging transverse and longitudinal relaxation rates at 3.0 T in neonatal brain, the p relationship between these rates, and their potential use for gray matter (G),versus-M white matter (WM) tissue discrimination. MATERIALS AND METHODS: I Informed parental consent for performance of imaging procedures was obtained in each infant. Informed consent for retrospective image analysis was not required; ethics approval was obtained from institutional review board. At 3.0 T, R1 and R2 were measured in brain regions (frontal WM, posterior WM, periventricular WM, frontal GM, posterior GM, basal ganglia, and thalamus) in …


Endocytic Intermediates Involved With The Intracellular Trafficking Of A Fluorescent Cellular Prion Protein, Ac Magalhaes, Ja Silva, Vr Martins, Vf Prado, Ssg Ferguson, Mv Gomez, Rr Brentani, Mam Prado Sep 2002

Endocytic Intermediates Involved With The Intracellular Trafficking Of A Fluorescent Cellular Prion Protein, Ac Magalhaes, Ja Silva, Vr Martins, Vf Prado, Ssg Ferguson, Mv Gomez, Rr Brentani, Mam Prado

Anatomy and Cell Biology Publications

We have investigated the intracellular traffic of PrPc, a glycosylphosphatidylinositol (GPI)-anchored protein implicated in spongiform encephalopathies. A fluorescent functional green fluorescent protein (GFP)-tagged version of PrPc is found at the cell surface and in intracellular compartments in SN56 cells. Confocal microscopy and organelle-specific markers suggest that the protein is found in both the Golgi and the recycling endosomal compartment. Perturbation of endocytosis with a dynamin I-K44A dominant-negative mutant altered the steady-state distribution of the GFP-PrPc, leading to the accumulation of fluorescence in unfissioned endocytic intermediates. These pre-endocytic intermediates did not seem to accumulate GFP-GPI, a minimum GPI-anchored protein, suggesting that …