Role of Astrocytes in Delayed Neuronal Death: GLT-1 and its Novel Regulation by MicroRNAs

Abstract

Astrocytes have been shown to protect neurons from delayed neuronal death and increase their survival in cerebral ischemia. One of the main mechanisms of astrocyte protection is rapid removal of excess glutamate from synaptic sites by astrocytic plasma membrane glutamate transporters such as GLT-1/EAAT-2, reducing excitotoxicity. Astrocytic mitochondrial function is essential for normal GLT-1 function. Manipulating astrocytic mitochondrial and GLT-1 function is thus an important strategy to enhance neuronal survival and improve outcome following cerebral ischemia. Increasing evidence supports the involvement of microRNAs (miRNA), some of them being astrocyte-enriched, in the regulation of cerebral ischemia. This chapter will first update the information about astrocytes, GLT-1, astrocytic mitochondria, and delayed neuronal death. Then we will focus on two recently reported astrocyte-enriched miRNAs (miR-181 and miR-29 families), their effects on astrocytic mitochondria and GLT-1 as well as on outcome after cerebral ischemia.