The role of phospholipases A2 in schizophrenia

Abstract

A range of neurotransmitter systems have been implicated in the pathogenesis of schizophrenia based on the antidopaminergic activities of antipsychotic medications, and chemicals that can induce psychotic-like symptoms, such as ketamine or PCP. Such neurotransmitter systems often mediate their cellular response via G-protein-coupled release of arachidonic acid (AA) via the activation of phospholipases A2 (PLA2s). The interaction of three PLA2s are important for the regulation of the release of AA -phospholipase A2 Group 2 A, phospholipase A2 Group 4A and phospholipase A2 Group 6A. Gene variations of these three key enzymes have been associated with schizophrenia with conflicting results. Preclinical data suggest that the activity of these three enzymes are associated with monoaminergic neurotransmission, and may contribute to the differential efficacy of antipsychotic medications, as well as other biological changes thought to underlie schizophrenia, such as altered neurodevelopment and synaptic remodelling. We review the evidence and discuss the potential roles of these three key enzymes for schizophrenia with particular emphasis on published association studies.

BanI polymorphism of cytosolic phospholipase A2 gene and somatic symptoms in medication-free acute depressed patients

“…The endogenous metabolism of PGs are modulated by PUFAs [39], and cPLA2 is the key enzyme to catalyze the release of AA, the precursor of PGE2, from membrane phospholipids [40]. AA is then converted to PGE2 by COX-2.…”

Schizophrenia: From the brain to peripheral markers. A consensus paper of the WFSBP task force on biological markers

“…Interestingly, both VGF (nerve growth factor-inducible neuropeptide) and transthyretin, demonstrated parallel alterations in postmortem brain tissue of patients with schizophrenia. Several CSF proteins and lipids pathways are important in brain physiology (Wenk 2005) and have the potential of being useful biomarkers of schizophrenia (Law et al 2006; Table IV). While changes are reported for these molecules, usually, only small sample sizes were studied, pointing to the need of more rigorous clinical studies.…”

Phosphorus Spectroscopy (31P MRS) of the Brain in Psychiatric Disorders

“…Such is the case seen in many studies of patients with schizophrenia. [83][84][85] Conclusion 31 P MRS can provide a wealth of biochemical information on high-energy phosphates, membrane precursors, and metabolites that are essential for cellular survival and impact the overall state of health of the cell. Fusing biochemical knowledge with the exquisite physics of 31 P MRS can yield unique insight into the energetic and homeostatic nature of the cells of the brain.…”