Biology subjects

Menard, F.

Publications and source records attributed to Menard, F..

4 recordsLinked to original sources

bioRxiv2021

Aminooxadiazolyl kainic acid reveals that kainic acid receptors contribute to astrocytoma glutamate signaling

The excitatory neurotransmitter glutamate triggers a Ca2+ rise and the extension of processes in astrocytes. Our results suggest that kainic acid receptors (KAR) can independently initiate glutamate signaling in astrocytoma U118-MG cells. The natural product kainic acid triggered glioexcitablity in cells and was inhibited by the KAR antagonist CNQX, but its activity was lower than glutamate on KARs. We created a new heteroaryl kainoid based on rational design: aminooxadiazolyl kainic acid 1 (AODKA). AODKA induced a larger calcium influx and a faster processes extension than kainic acid in U118-MG cells. AODKA is a new tool to study KAR activity in the nervous system. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=145 SRC="FIGDIR/small/426948v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@1b63f72org.highwire.dtl.DTLVardef@1ff92c4org.highwire.dtl.DTLVardef@1fcb212org.highwire.dtl.DTLVardef@10ed76e_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2020

Design of an imaging probe to monitor real-time redistribution of L-type voltage gated calcium channels in astrocytic glutamate signalling

PurposeIn the brain, astrocytes are non-excitable cells that undergo rapid morphological changes when stimulated by the excitatory neurotransmitter glutamate. We developed a chemical probe to monitor how glutamate affects the density and distribution of astrocytic L-type voltage-gated calcium channels (LTCC). ProceduresThe imaging probe FluoBar1 was created from a barbiturate ligand modified with a fluorescent coumarin moiety. The probe selectivity was examined with colocalization analyses of confocal fluorescence imaging in U118-MG and transfected COS-7 cells. Living cells treated with 50 nM FluoBar1 were imaged in real time to reveal changes in density and distribution of astrocytic LTCCs upon exposure to glutamate. ResultsFluoBar1 was synthesized in ten steps. The selectivity of the probe was demonstrated with immunoblotting and confocal imaging of immunostained cells expressing the CaV1.2 isoform of LTCCs proteins. Applying FluoBar1 to astrocyte model cells U118-MG allowed us to measure a 5-fold increase in fluorescence density of LTCCs upon glutamate exposure. ConclusionsImaging probe FluoBar1 allows the real-time monitoring of LTCCs in living cells, revealing for first time that glutamate causes a rapid increase of LTCC membranar density in astrocyte model cells. FluoBar1 may help tackle previously intractable questions about LTCC dynamics in cellular events.

neuroscience↗

bioRxiv2019

L-type voltage-gated calcium channel modulators inhibit glutamate-induced morphology in astrocytoma cells

The excitatory neurotransmitter glutamate evokes physiological responses within the astrocytic network that lead to fine morphological dynamics. However, the mechanism by which astrocytes couple glutamate sensing with cellular calcium rise remains unclear. Employing natural properties of U118-MG astrocytoma cells, we tested a possible connection between L-type voltage-gated calcium channels (Cav) and glutamate receptors. Using live confocal imaging and pharmacological inhibitors, the extension of U118-MG processes upon glutamate exposure are shown to depend mainly on extracellular calcium entry via L-type Cavs. Inhibitors of the Cav 1 protein, decreased astrocytic filopodia extension; while, gabapentinoids, ligands of the Cavs 2{delta} auxiliary subunit blocked all process growth. This study suggests that 2{delta} is the main contributor to Cavs role in glutamate-dependent filopodiagenesis. It opens new avenues of research on the role of 2{delta} in neuron-astrocyte glutamate signaling and neurochemical signaling at tripartite synapses.

neuroscience↗

bioRxiv2019

Does evolution design robust food webs?

Theoretical works that use a dynamical approach to study the ability of ecological communities to resist perturbations are largely based on randomly generated ecosystem structures. In contrast, we propose here to asses the robustness of food webs drawn from ecological and evolutionary processes with the use of community evolution models. In a first part, with the use of Adaptive Dynamics theoretical framework, we generate a variety of diversified food webs by solely sampling different richness levels of the environment as a control parameter, and obtain networks that satisfactory compare with empirical data. This allows us to highlight the complex, structuring role of the environmental richness during the evolutionary emergence of food webs. In a second part, we study the short-term ecological responses of food webs to swift changes in their customary environmental richness condition. We reveal a strong link between the environmental conditions that attended food webs evolutionary constructions and their robustness to environmental perturbations. When focusing on emergent properties of our evolved food webs, especially connectance, we highlight results that seem to contradict the current paradigm. Among these food webs, the most connected appear to be the less robust to sudden depletion of the environmental richness that constituted their evolutionary environment. Otherwise, we appraise the \"adaptation\" of food webs, by examining how they perform after being suddently immersed in an environment of modified richness level, in comparison with a trophic network that experienced this latter environmental condition all along its evolution.

ecology↗