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

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

Walking in the cement forest: a health enhancement and pedometer-determined ambulatory (HEPA) program in Hong Kong

Congress Theme: A Celebration of Diversity and Inclusion in Active AgeingThis journal suppl.entitled: Supplement issue: Abstracts for the 8th World Congress on Ageing and Physical Activitypublished_or_final_versionThe 8th Annual World Congress on Active Ageing (WCAA): A Celebration of Diversity and Inclusion in Active Ageing, Glasgow, Scotland, UK, 13 -17 August 2012. In Journal of Aging and Physical Activity, 2012, v. 20, Suppl., p. S226-S22

Walking in the High-rise City: A Health Enhancement and Pedometer-determined Ambulatory (HEPA) Program in Hong Kong

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Interleukin-6 Is a Potential Biomarker for Severe Pandemic H1N1 Influenza A Infection

Pandemic H1N1 influenza A (H1N1pdm) is currently a dominant circulating influenza strain worldwide. Severe cases of H1N1pdm infection are characterized by prolonged activation of the immune response, yet the specific role of inflammatory mediators in disease is poorly understood. The inflammatory cytokine IL-6 has been implicated in both seasonal and severe pandemic H1N1 influenza A (H1N1pdm) infection. Here, we investigated the role of IL-6 in severe H1N1pdm infection. We found IL-6 to be an important feature of the host response in both humans and mice infected with H1N1pdm. Elevated levels of IL-6 were associated with severe disease in patients hospitalized with H1N1pdm infection. Notably, serum IL-6 levels associated strongly with the requirement of critical care admission and were predictive of fatal outcome. In C57BL/6J, BALB/cJ, and B6129SF2/J mice, infection with A/Mexico/4108/2009 (H1N1pdm) consistently triggered severe disease and increased IL-6 levels in both lung and serum. Furthermore, in our lethal C57BL/6J mouse model of H1N1pdm infection, global gene expression analysis indicated a pronounced IL-6 associated inflammatory response. Subsequently, we examined disease and outcome in IL-6 deficient mice infected with H1N1pdm. No significant differences in survival, weight loss, viral load, or pathology were observed between IL-6 deficient and wild-type mice following infection. Taken together, our findings suggest IL-6 may be a potential disease severity biomarker, but may not be a suitable therapeutic target in cases of severe H1N1pdm infection due to our mouse data

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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