The role of proheparanase in synaptic plasticity at the hippocampus

Abstract no. P-110Perineuronal heparan sulfate (HS) moieties are implicated in the modulation of neurotransmission by controlling the functional properties of AMPA-type glutamate receptors. We hypothesize that neuronal mechanisms modulate peri-synaptic HS level, thereby regulating synaptic strength and plasticity. To address this, basal synaptic strength and long-term changes in synaptic efficacy in the Schaffer collateral pathway of the rat hippocampus were assessed in relation to strategies that perturb peri-synaptic HS. In hippocampal slices, heparitinase treatment led to dose-dependent attenuation of long-term potentiation (LTP) in correlation with loss of perineuronal HS …postprin

Regulatory role of proheparanase with peri-synaptic heparan sulfate proteoglycan and AMPA-type glutamate receptor in synaptic plasticity

Poster Presentation: P59AMPA-type glutamate receptors (AMPAR) govern excitatory synaptic transmission. Perineuronal heparan sulfates (HS) have been implicated in controlling the open-state of AMPAR. Our finding of neuronal heparanase expression in adult rats led us to test (1) if neuronal heparanase is secreted and (2) if the secreted form acts on perineuronal HS to modulate synaptic plasticity. Neuronal secretion of heparanase was triggered by phorbol ester of rat hippocampal neurons in culture. Western blot analysis of the secreted product revealed enzymatically inactive proheparanase, but not the enzymatically active heparanase. Synaptosomes prepared from phorbol ester-treated rat cortexslices showed enrichment in proheparanase; co-immunoprecipitation studies further showed association of AMPAR subunits (GluA1 and GluA2/3) with both syndecan-3 (a transmembrane HS-proteoglycan) and proheparanase, suggesting their partnership in the peri-synaptic environment. Treatment of hippocampal neurons in culture with recombinant proheparanase triggered internalization of proheparanase, perineuronal HS-proteoglycans and AMPARs, suggesting their clustering as a functional complex. Heparitinase pre-treatment of hippocampal neuron cultures reduced proheparanase-induced internalization of AMPARs, suggesting that the HS moiety is critical for effecting the partnership. Treatment of hippocampal slices with recombinant proheparanase resulted in down-regulation of both basal synaptic strength and LTP at Schaffer collateral synapses. These results reveal a novel role of neuronal proheparanase in resetting AMPAR and perineuronal HS levels at the synapse and thus the modulation of synaptic plasticity.postprin

Successful radiation treatment of anaplastic thyroid carcinoma metastatic to the right cardiac atrium and ventricle in a pacemaker-dependent patient

Anaplastic thyroid carcinoma (ATC) is a rare, aggressive malignancy, which is known to metastasize to the heart. We report a case of a patient with ATC with metastatic involvement of the pacemaker leads within the right atrium and right ventricle. The patient survived external beam radiation treatment to his heart, with a radiographic response to treatment. Cardiac metastases are usually reported on autopsy; to our knowledge, this is the first report of the successful treatment of cardiac metastases encasing the leads of a pacemaker, and of cardiac metastases from ATCs, with a review of the pertinent literature

Neuronal and astrocytic proheparanase: Insights on its role in regulating synaptic transmission in central nervous system

Organised by the Research Centre of Heart, Brain, Hormone and Healthy Aging, the University of Hong Kon

Role of neuronal and astrocytic proheparanase in regulating synaptic strength in rat hippocampus

Conference Theme: Science and Aging: An Era of Discover

Role of proheparanase in regulating synaptic plasticity in rat hippocampus

Conference Theme: A Decade of Positive Agin

Neuronal and astrocytic proheparanase: Roles in regulating synaptic strength in rat hippocampus

Excitability / Synaptic Transmission / Network Functions: B.7.F Synaptic Plasticity - Neuromodulators ; Poster Presentation 2: Board no. B087 - abstract no. 76

Role of heparanase in synaptic plasticity at the hippocampus and the vestibular nucleus

Poster Session: IV-2 Synapse & neural cellular communication: Others: P1AM-11-4This journal supplement is proceedings of the 36th International Congress of Physiological Sciences (IUPS2009)The 36th International Congress of Physiological Sciences (IUPS2009), Kyoto, Japan, 27 July-1 August 2009. In Journal of Physiological Sciences, 2009, v. 59 suppl. 1, p. 14

Regulation of AMPA-type glutamate receptor trafficking by proheparanase in synaptic plasticity

Poster Session 870 - Synaptic Plasticity: Homeostatic II - Theme B: Neural Excitability, Synapses, and Glia: Cellular Mechanisms: no. 870.09/D41Synaptic plasticity is the activity-dependent modification of the strength of synaptic transmission. Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors (AMPARs) at excitatory synapse mediate fast neurotransmission. Membrane depolarization of postsynaptic neurons then triggers Ca2+ influx that upregulates membrane insertion of AMPARs, resulting in long-lasting potentiation of excitatory post-synaptic potential. Perineuronal heparan sulfates (HS) are implicated in controlling the open-state of AMPARs for the maintenance of synaptic strength. Treatment of hippocampal slice cultures with heparitinase, a bacterial HS-cleaving enzyme, decreases hippocampal LTP on a dose-dependent manner. Our finding of neuronal expression of heparanase, a mammalian HS-cleaving enzyme, led us to test if (1) neuronal heparanase is secreted as the pro-form or the active form and (2) if binding of the secreted form to perineuronal HS plays a role in synaptic plasticity. Hippocampal neurons in culture were treated with phorbol ester to stimulate secretion from vesicular stores. Western blot analysis of secreted material revealed the pro-form. Synaptosome preparations also indicated enrichment in proheparanse. Synaptosome preparations subjected to co-immunoprecipitation studies revealed AMPAR subunits (GluA1 and GluA2/3) binding to both syndecan-3 (a transmembrane HS proteoglycan of neurons) and proheparanase, suggesting their clustering in a functional complex. Treatment of hippocampal neuron cultures with recombinant proheparanase triggered internalization of proheparanase together with perineuronal HS-proteoglycans and AMPARs. Treatment of hippocampal slices with recombinant proheparanase resulted in declines in both basal synaptic strength and LTP. Taken together, the results indicate neuronal secretion of proheparanase as a novel mechanism that contributes to synaptic plasticity by re-setting AMPAR level at the synapse.link_to_OA_fulltextThe 2011 Annual Meeting of the Society for Neuroscience, Washington, D.C., 12-16 November 2011. In Abstract Book of Neuroscience, 2011, p. 244-24