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GLAST Activity is Modified by Acute Manganese Exposure in Bergmann Glial Cells

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Abstract

Glutamate is the major excitatory amino acid neurotransmitter in the vertebrate brain. It exerts its actions through the activation of specific plasma membrane receptors expressed in neurons and glial cells. Overactivation of glutamate receptors results in neuronal death, known as excitotoxicity. A family of sodium-dependent glutamate transporters enriched in glial cells are responsible of the vast majority of the removal of this amino acid form the synaptic cleft. Therefore, a precise and exquisite regulation of these proteins is required not only for a proper glutamatergic transmission but also for the prevention of an excitotoxic insult. Manganese is a trace element essential as a cofactor for several enzymatic systems, although in high concentrations is involved in the disruption of brain glutamate homeostasis. The molecular mechanisms associated to manganese neurotoxicity have been focused on mitochondrial function, although energy depletion severely compromises the glutamate uptake process. In this context, in this contribution we analyze the effect of manganese exposure in glial glutamate transporters function. To this end, we used the well-established model of chick cerebellar Bergmann glia cultures. A time and dose dependent modulation of [3H]-d-aspartate uptake was found. An increase in the transporter catalytic efficiency, most probably linked to a discrete increase in the affinity of the transporter was detected upon manganese exposure. Interestingly, glucose uptake was reduced by this metal. These results favor the notion of a direct effect of manganese on glial cells, this in turn alters their coupling with neurons and might lead to changes in glutamatergic transmission.

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Acknowledgements

ME and JSV were supported by Conacyt-Mexico PhD scholarships. This work was funded by Conacyt-Mexico (255087) Grant to AO.

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Authors and Affiliations

  1. Departamento de Toxicología, Centro de Investigación Y de Estudios Avanzados del IPN, Apartado Postal 14-740, 07360, Ciudad de Mexico, Mexico

    Miguel Escalante, Jazmín Soto-Verdugo, Luisa C. Hernández-Kelly, Dinorah Hernández-Melchor, Esther López-Bayghen & Arturo Ortega

  2. Instituto de Investigaciones Oceanológicas, Universidad Autónoma de Baja California, 22860, Ensenada, Baja California, Mexico

    Tatiana N. Olivares-Bañuelos

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  1. Miguel Escalante
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Escalante, M., Soto-Verdugo, J., Hernández-Kelly, L.C. et al. GLAST Activity is Modified by Acute Manganese Exposure in Bergmann Glial Cells. Neurochem Res 45, 1365–1374 (2020). https://doi.org/10.1007/s11064-019-02848-8

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