Pituitary Adenylate Cyclase-Activating Polypeptide Orchestrates Neuronal Regulation Of The Astrocytic Glutamate-Releasing Mechanism System x_c⁻

Authors

Linghai Kong, Marquette University
Rebecca Albano, Marquette University
Aric Madayag, Marquette UniversityFollow
Nicholas Raddatz, Marquette University
John R. Mantsch, Marquette UniversityFollow
Sujean Choi, Marquette UniversityFollow
Doug Lobner, Marquette UniversityFollow
David A. Baker, Marquette UniversityFollow

Document Type

Article

Language

eng

Publication Date

5-2016

Publisher

Wiley

Source Publication

Journal of Neurochemistry

Source ISSN

0022-3042

Original Item ID

doi: 10.1111/jnc.13566

Abstract

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 x_c^-(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.

Comments

Accepted version. Journal of Neurochemistry, Vol. 137, No. 3 (May 2016): 384-393. DOI. © 2016 Wiley. Used with permission.

This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for self-archiving.

Recommended Citation

Kong, Linghai; Albano, Rebecca; Madayag, Aric; Raddatz, Nicholas; Mantsch, John R.; Choi, Sujean; Lobner, Doug; and Baker, David A., "Pituitary Adenylate Cyclase-Activating Polypeptide Orchestrates Neuronal Regulation Of The Astrocytic Glutamate-Releasing Mechanism System x_c⁻" (2016). Biomedical Sciences Faculty Research and Publications. 148.
https://epublications.marquette.edu/biomedsci_fac/148