Showing papers by "Michael W. Salter published in 2006"
TL;DR: A fundamental role for insulin-responsive TRPV1(+) sensory neurons in beta cell function and diabetes pathoetiology is uncovered and delivered by intra-arterial injection into the NOD pancreas reverses abnormal insulin resistance, insulitis, and diabetes for weeks.
349 citations
TL;DR: The PSD‐95–Src SH2 domain interaction suppresses Src‐mediated NMDAR upregulation, a finding that may be of broad importance for synaptic transmission and plasticity.
Abstract: The tyrosine kinase Src upregulates the activity of the N-methyl-D-aspartate subtype of glutamate receptor (NMDAR) and tyrosine phosphorylation of this receptor is critical for induction of NMDAR-dependent plasticity of synaptic transmission A binding partner for Src within the NMDAR complex is the protein PSD-95 Here we demonstrate an interaction of PSD-95 with Src that does not require the well-characterized domains of PSD-95 Rather, we show binding to Src through a 12-amino-acid sequence in the N-terminal region of PSD-95, a region not previously known to participate in protein–protein interactions This region interacts directly with the Src SH2 domain Contrary to typical SH2 domain binding, the PSD-95–Src SH2 domain interaction is phosphotyrosine-independent Binding of the Src-interacting region of PSD-95 inhibits Src kinase activity and reduces NMDAR phosphorylation Intracellularly administering a peptide matching the Src SH2 domain-interacting region of PSD-95 depresses NMDAR currents in cultured neurons and inhibits induction of long-term potentiation in hippocampus Thus, the PSD-95–Src SH2 domain interaction suppresses Src-mediated NMDAR upregulation, a finding that may be of broad importance for synaptic transmission and plasticity
64 citations
TL;DR: The relationships between clinical symptoms and experimental models of peripheral neuropathic pain are described, and a framework for understanding the potential mechanisms that involve primary neuronal dysfunction as well as pathological changes in neuron‐glial signaling is provided.
Abstract: Peripheral neuropathic pain is the most debilitating of all clinical pain syndromes and affects a large and growing number of people worldwide. There are diverse causes for peripheral neuropathic pain, which may be experienced after traumatic nerve injury or from diseases that affect peripheral nerves, such as diabetes, HIV/AIDS, and cancer, and it can also result from toxic chemicals, such as cancer chemotherapy agents. Despite these varying causes, it is clear that neuropathic pain is due to persistent pathological alterations resulting in hyperexcitability in the peripheral and central nervous systems, and it is the neuropathology that must be targeted for effective therapy of which there is none presently available. Mechanistically, neuropathic pain is distinct from acute pain and inflammatory pain, for which many effective therapies are known. In this review, we describe the relationships between clinical symptoms and experimental models of peripheral neuropathic pain, and we provide a framework for understanding the potential mechanisms that involve primary neuronal dysfunction as well as pathological changes in neuron-glial signaling. Drug Dev. Res. 67:289–301, 2006. © 2006 Wiley-Liss, Inc.
18 citations
TL;DR: The pericytes, small cells that wrap around the capillaries close to active nerve cells, are likely to contribute to the signals detected in brain imaging techniques, and could also provide a target for therapy in disorders of brain blood flow.
Abstract: Non-invasive imaging techniques that reveal those parts of the brain that are active by detecting the increased blood flow that supplies extra glucose and oxygen to active nerve cells. Until now it was assumed that blood flow is controlled by the contraction of smooth muscle around large blood vessels called arterioles. Now an additional level of blood flow control has been discovered, downstream of arterioles. This control is exerted by the pericytes, small cells that wrap around the capillaries close to active nerve cells. The pericytes, that act by squeezing the capillary to reduce blood flow though it, are likely to contribute to the signals detected in brain imaging techniques, and could also provide a target for therapy in disorders of brain blood flow.
9 citations
University of Pittsburgh1, Harvard University2, Washington University in St. Louis3, Queen's University4, University of Bristol5, University of Kentucky6, University of Calgary7, University of British Columbia8, University of Porto9, New York University10, University of Florida11, Kyushu University12, Nihon University13, University of Toronto14, Seoul National University15, Sapporo Medical University16, Tokyo University of Agriculture17, Baylor College of Medicine18, Niigata University19, Johns Hopkins University20, Emory University21, McGill University22, University of Alberta23, University of Maryland, Baltimore24, University of California, Irvine25, National Institutes of Health26, University at Buffalo27, University of Chicago28, Indiana University29, University of Saskatchewan30
TL;DR: The goal for this meeting is to promote future active scientific collaborations and improve human health through fundamental basic neuroscience researches.
Abstract: Understanding basic neuronal mechanisms hold the hope for future treatment of brain disease. The 1st international conference on synapse, memory, drug addiction and pain was held in beautiful downtown Toronto, Canada on August 21–23, 2006. Unlike other traditional conferences, this new meeting focused on three major aims: (1) to promote new and cutting edge research in neuroscience; (2) to encourage international information exchange and scientific collaborations; and (3) to provide a platform for active scientists to discuss new findings. Up to 64 investigators presented their recent discoveries, from basic synaptic mechanisms to genes related to human brain disease. This meeting was in part sponsored by Molecular Pain, together with University of Toronto (Faculty of Medicine, Department of Physiology as well as Center for the Study of Pain). Our goal for this meeting is to promote future active scientific collaborations and improve human health through fundamental basic neuroscience researches. The second international meeting on Neurons and Brain Disease will be held in Toronto (August 29–31, 2007).
5 citations
01 Jan 2006
TL;DR: Esta arquitectura sinaptica anatomica aporta el sustrato para que se produzca una transferencia exacta oficial sobre el inicio, duracion, localizacion and calidad of los estimulos nocivos perifericos.
Abstract: La entrada sensitiva que se genera en las neuronas sensitivas primarias por estimulos perifericos nocivos o intensos se transfiere, a traves de sus axones centrales, a neuronas de segundo orden de la medula espinal. Los contactos sinapticos entre las terminales centrales aferentes y las neuronas del asta posterior estan muy organizadas, segun la topografia, para reflejar su localizacion, y el tipo de fibras sensitivas. Esta arquitectura sinaptica anatomica –junto con la transmision sinaptica inhibidora y excitadora rapida provocada por las aferencias primarias– aporta el sustrato para que se produzca una transferencia exacta de la informacion sobre el inicio, duracion, localizacion y calidad de los estimulos nocivos perifericos.