The Contribution of System Xc-to Prefrontal Cortical Mediated Behaviors Associated with Schizophrenia
Year: 2012
Type: dissertation
Abstract: Schizophrenia is a debilitating disorder involving impaired cognition, disorganized thinking, and auditory hallucinations that has a tremendous unmet medical need, potentially because current antipsychotics insufficiently target the pathophysiology of the disease. The neural basis of schizophrenia appears to involve abnormal activity within the dorsolateral prefrontal cortex (PFC) in which efferent neurons exhibit disorganized firing patterns. Synchronization of cortical activity is regulated by complex inter-neuronal connections, which is compromised in schizophrenia. Schizophrenic’s exhibit reduced PFC volume that may reflect reduced arborization leading to diminished inter-neuronal connectivity. An unexplored explanation is that reduced volume reflects changes in astrocytes, cells positioned to control synchronized firing at up to 100K synapses. Glutamate release, including from system xc- which exchanges one intracellular glutamate for an extracellular cystine, is emerging as a component of astrocytic neuronal regulation and is altered in the PFC of schizophrenics. To determine the importance of system xc- dysregulation, we examined the impact of increased or decreased activity to glutamate levels in the PFC and PFC mediated behaviors that are
Author: Victoria Lutgen
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W119010206