Medicine and Health Sciences Commons^™

Behavioral Assessment Of Acute Inhibition Of System XC - In Rats, Victoria Lutgen, Jon M. Resch, Krista Qualmann, Nicholas J. Raddatz, Cristina Panhans, Ellen M. Olander, Linghai Kong, Sujean Choi, John R. Mantsch, David A. Baker

Biomedical Sciences Faculty Research and Publications

Rationale

Gaps in our understanding of glutamatergic signaling may be key obstacles in accurately modeling complex CNS diseases. System x_c ^- is an example of a poorly understood component of glutamate homeostasis that has the potential to contribute to CNS diseases.

Objectives

This study aims to determine whether system x_c ^- contributes to behaviors used to model features of CNS disease states.

Methods

In situ hybridization was used to map mRNA expression of xCT throughout the brain. Microdialysis in the prefrontal cortex was used to sample extracellular glutamate levels; HPLC was used to measure extracellular glutamate and tissue …

Time Course Of Cocaine-Induced Behavioral And Neurochemical Plasticity, Victoria Lutgen, Linghai Kong, Kristen S. Kau, Aric Madayag, John Mantsch, David A. Baker

Biomedical Sciences Faculty Research and Publications

Factors that result in augmented reinstatement, including increased withdrawal period duration and high levels of cocaine consumption, may provide insight into relapse vulnerability. The neural basis of augmented reinstatement may arise from more pronounced changes in plasticity required for reinstatement and/or the emergence of plasticity expressed only during a specific withdrawal period or under specific intake conditions. In this study, we examined the impact of withdrawal period duration and cocaine intake on the magnitude of cocaine-primed reinstatement and extracellular glutamate in the nucleus accumbens, which has been shown to be required for cocaine-primed reinstatement. Rats were assigned to self-administer under …

Inhibition Of Food Intake By Pacap In The Hypothalamic Ventromedial Nuclei Is Mediated By Nmda Receptors, Jon M. Resch, Brian Maunze, Kailynn A. Phillips, Sujean Choi

Biomedical Sciences Faculty Research and Publications

Central injections of pituitary adenylate cyclase-activating polypeptide (PACAP) into the ventromedial nuclei (VMN) of the hypothalamus produce hypophagia that is dependent upon the PAC1 receptor; however, the signaling downstream of this receptor in the VMN is unknown. Though PACAP signaling has many targets, this neuropeptide has been shown to influence glutamate signaling in several brain regions through mechanisms involving NMDA receptor potentiation via activation of the Src family of protein tyrosine kinases. With this in mind, we examined the Src-NMDA receptor signaling pathway as a target for PACAP signaling in the VMN that may mediate its effects on feeding behavior. …

Fgf-2 Induces Neuronal Death Through Upregulation Of System Xc-, Xiaoqian Liu, Rebecca Albano, Doug Lobner

Biomedical Sciences Faculty Research and Publications

The cystine/glutamate antiporter (system xc-) transports cystine into cell in exchange for glutamate. Fibroblast growth factor-2 (FGF-2) upregulates system xc- selectively on astrocytes, which leads to increased cystine uptake, the substrate for glutathione production, and increased glutamate release. While increased intracellular glutathione can limit oxidative stress, the increased glutamate release can potentially lead to excitotoxicity to neurons. To test this hypothesis, mixed neuronal and glial cortical cultures were treated with FGF-2. Treatment with FGF-2 for 48 h caused a significant neuronal death in these cultures. Cell death was not observed in neuronal-enriched cultures, or astrocyte-enriched …