Format of Original
10 p.; 26 cm
Journal of Neurochemistry
Original Item ID
doi: 10.1111/jnc.13566; Shelves: QP 351 .J57 2016 v. 137, Memorial Periodicals; PubMed Central, PMCID: 26851652
Glutamate signaling is achieved by an elaborate network involving neurons and astrocytes. Hence, it is critical to better understand how neurons and astrocytes interact to coordinate the cellular regulation of glutamate signaling. In these studies, we used rat cortical cell cultures to examine whether neurons or releasable neuronal factors were capable of regulating system xc-(Sxc), a glutamate-releasing mechanism that is expressed primarily by astrocytes and has been shown to regulate synaptic transmission. We found that astrocytes cultured with neurons or exposed to neuronal-conditioned media displayed signiﬁcantly higher levels of Sxc activity. Next, we demonstrated that the pituitary adenylate cyclase-activating polypeptide (PACAP) may be a neuronal factor capable of regulating astrocytes. In support, we found that PACAP expression was restricted to neurons, and that PACAP receptors were expressed in astro-cytes. Interestingly, blockade of PACAP receptors in cultures comprised of astrocytes and neurons signiﬁcantly decreased Sxc activity to the level observed in puriﬁed astrocytes, whereas application of PACAP to puriﬁed astrocytes increased Sxc activity to the level observed in cultures comprised of neurons and astrocytes. Collectively, these data reveal that neurons coordinate the actions of glutamate-related mechanisms expressed by astrocytes, such as Sxc, a process that likely involves PACAP.