Faculty Collaboration Database

Pituitary Adenylate cyclase-activating polypeptide orchestrates neuronal regulation of the astrocytic glutamate-releasing mechanism system xc (.). J Neurochem 2016 May;137(3):384-93

Date

02/07/2016

Pubmed ID

26851652

Pubmed Central ID

PMC4878137

DOI

10.1111/jnc.13566

Scopus ID

2-s2.0-84963626414 (requires institutional sign-in at Scopus site)   12 Citations

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 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 astrocytes. 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. A critical gap in modeling excitatory signaling is how distinct components of the glutamate system expressed by neurons and astrocytes are coordinated. In these studies, we found that system xc (-) (Sxc), a glutamate release mechanism expressed by astrocytes, is regulated by releasable neuronal factors including PACAP. This represents a novel form of neuron-astrocyte communication, and highlights the possibility that pathological changes involving astrocytic Sxc may stem from altered neuronal activity.

Author List

Kong L, Albano R, Madayag A, Raddatz N, Mantsch JR, Choi S, Lobner D, Baker DA

Authors

Sujean Choi PhD in the School of Allied Health department at Marquette University
John Mantsch PhD Chair, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amino Acid Transport Systems, Acidic
Animals
Astrocytes
Cystine
Female
Glutamic Acid
Neurons
Pituitary Adenylate Cyclase-Activating Polypeptide
Pregnancy
Rats
Rats, Sprague-Dawley
Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
Synaptic Transmission
Up-Regulation