Pyridazine-derivatives Enhance Structural and Functional Plasticity of Tripartite Synapse Via Activation of Local Translation in Astrocytic Processes.

ABSTRACT: Excitatory amino acid transporter 2 (EAAT2) is primarily located in perisynaptic astrocytic processes (PAP) where it plays a critical role in synaptic glutamate homeostasis. Dysregulation of EAAT2 at the translational level has been implicated in a myriad of neurological diseases. We previously discovered that pyridazine analogs can activate EAAT2 translation. Here, we sought to further refine the site and mechanism of compound action. We found that in vivo, compound treatment increased EAAT2 expression only in the PAP of astrocytes where EAAT2 mRNA also was identified. Direct application of compound to isolated PAP induced de novo EAAT2 protein synthesis, indicating that compound activates translation locally in the PAP. Using a screening process, we identified a set of PAP proteins that

SUBMITTER: Foster JB 

PROVIDER: S-EPMC6667176 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature