The 2019 Novel Corona virus infection (COVID 19) is an ongoing public health emergency of international focus. Significant gaps persist in our knowledge of COVID 19 epidemiology, transmission dynamics, investigation tools and management, despite (or possibly because of) the fact that the outbreak is an unprecedented global threat. On the positive side, enough is currently known about the epidemic process to permit the construction of mathematical predictive models. In our work, we adapt a traditional SEIR epidemic model to the specific dynamic compartments and epidemic parameters of COVID 19, as it spreads in an age-heterogeneous community. We analyze management strategies of the epidemic course (as they were implemented through lockdown and reopening procedures in many of the US states and countries worldwide); however, to more clearly illustrate ideas, we focus on the example of a small scale college town community, with the timeline of control measures introduced in the state of New York. We generate predictions, and assess the efficiency of these control measures (closures, mobility restrictions, social distancing), in a sustainability context.
Glutamate transporters preserve the spatial specificity of synaptic transmission by limiting glutamate diffusion away from the synaptic cleft, and prevent excitotoxicity by keeping the extracellular concentration of glutamate at low nanomolar levels. Glutamate transporters are abundantly expressed in astrocytes, and previous estimates have been obtained about their surface expression in astrocytes of the rat hippocampus and cerebellum. Analogous estimates for the mouse hippocampus are currently not available. In this work, we derive the surface density of astrocytic glutamate transporters in mice of different ages via quantitative dot blot. We find that the surface density of glial glutamate transporters is similar in 7-8 week old mice and rats. In mice, the levels of glutamate transporters increase until about 6 months of age and then begin to decline slowly. Our data, obtained from a combination of experimental and modeling approaches, point to the existence of stark differences in the density of expression of glutamate transporters across different sub-cellular compartments, indicating that the extent to which astrocytes limit extrasynaptic glutamate diffusion depends not only on their level of synaptic coverage, but also on the identity of the astrocyte compartment in contact with the synapse. Together, these findings provide information on how heterogeneity in the spatial distribution of glutamate transporters in the plasma membrane of hippocampal astrocytes my alter glutamate receptor activation out of the synaptic cleft.
Glutamate transporters preserve the spatial specificity of synaptic transmission by limiting glutamate diffusion away from the synaptic cleft, and prevent excitotoxicity by keeping the extracellular concentration of glutamate at low nanomolar levels. Glutamate transporters are abundantly expressed in astrocytes. Previous estimates in the rat hippocampus suggest that the surface density of glutamate transporters in astrocytic membranes is ~10,800 μm−2. Here, we estimate their surface density in astrocytic membranes of the mouse hippocampus, at different ages. By using realistic 3D Monte Carlo reaction-diffusion models, we show that varying the local glutamate transporter expression in astrocytes can alter profoundly the activation of extrasynaptic AMPA and NMDA receptors. Our findings show that the average density of astrocyte membranes and their surface density of glutamate transporters is higher in mice compared to rats, and increases with mouse age. There are stark differences in the density of expression of these molecules in different subcellular compartments, indicating that the extent to which astrocytes limit extrasynaptic glutamate diffusion depends not only on the level of astrocytic coverage, but also on the identity of the astrocyte compartment in contact with the synapse. Together, these findings provide information on the spatial distribution of glutamate transporters in the mouse hippocampus, which can be used in mathematical models of the spatiotemporal profile of extracellular glutamate after synaptic release.
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