Biomedical Seminar Series

“Glutamate transport, mitochondria and astrocytes: Implications for neurovascular coupling and stroke-mediated pathology” will be presented by  Michael Robinson, PhD, Professor of Pediatrics at the University of Pennsylvania School of Medicine.

Dr. Robinson’s seminar is open to the entire WSU Spokane campus and will be broadcast via Zoom to anyone interested. For questions, contact  Breezy Tottenhoff.  Please let Breezy know if you or a colleague would like to attend via videoconference.

Glutamate and aspartate are the predominant excitatory neurotransmitters in the mammalian CNS. These two excitatory amino acids (EAAs) mediate most of the rapid depolarization that occurs in the CNS. In fact, the levels of these transmitters are 1000- to 10,000-fold higher than those of many other important neurotransmitters, including dopamine, serotonin, and acetylcholine. Paradoxically, these EAAs are also potent neurotoxins, both in vivo and in vitro. In fact, excessive activation of EAA receptors contributes to the neuronal degeneration observed after acute insults to the CNS, such as stroke and head trauma. We are interested in the normal physiology of EAAs and the role of these transmitters in neurodegeneration. Our laboratory has focused on understanding the regulation of extracellular levels of EAAs because it is this pool of EAAs that is toxic to neurons. Extracellular concentrations of glutamate and aspartate are normally maintained in the low micromolar range by a family of sodium-dependent high affinity transporters that are present on both neurons and glial cells. Our laboratory has developed evidence that neurons induce and maintain expression of one of the astrocytic transporters critical for limiting excitotoxicity. We have begun to define the mechanisms that contribute to this regulation. Our laboratory has also found that the function of several of the transporter subtypes can be rapidly (within minutes) altered by activation of certain kinases. This regulation is associated with a redistribution of these transporters to/or from the plasma membrane (see the image below). The long term goal of the laboratory is to develop new strategies for limiting glutamate-mediated damage by understanding the endogenous mechanisms that clear this excitotoxin.