Astrocytes are one type of glia, the non-neuronal brain cells that have traditionally been thought of as support cells but are increasingly recognized for playing critical roles in normal neuronal transmission and in neurodegenerative disease. In amyotrophic lateral sclerosis (ALS), multiple lines of evidence now suggest that astrocyte dysfunction is a contributing factor in disease progression, according to Johns Hopkins researcher Jeffrey Rothstein, who spoke at a symposium focused on glial cells.
Much of the work centers on glutamate, an abundant neurotransmitter that turns on nerve cell firing. Too much glutamate is toxic to nerve cells; much of the secondary damage that often occurs after stroke or brain injury is due to unchecked release of glutamate, which damages and kills neurons.
One of the known functions of astrocytes is to take up excess glutamate from synapses where it might otherwise accumulate to toxic levels. Astrocytes are equipped with an array of so-called glutamate transporters to perform this cleanup. In ALS, there is “almost complete wipe-out” of glutamate transporters on astrocytes, Rothstein said, suggesting that these transporters are crucial in neuron death in the disease.
In new work, Rothstein’s lab has observed a similar disappearance from astrocytes of transporters for lactate, a protein thought to serve as a primary fuel source for neurons. Astrocytes are critical to this supply chain. But in mouse models of ALS, lactate transfer from astrocytes to neurons is essentially nil, and Rothstein sees the same thing in the spinal cords of ALS patients.
“This story is not yet complete, but here is another pathway that’s abnormal in astrocytes, which could lead to neuron death,” he said.