Phospholipase A(2) and the hypofrontality hypothesis of schizophrenia

Phospholipase A(2) (PLA(2)) catalyzes the hydrolysis of membrane phospholipids to release cytotoxic products such as lysophosphatidylcholine. In schizophrenia increased PLA(2) activity and an accelerated breakdown of membrane phospholipids have been reported. In neuronal do membranes PLA(2) modulates dopamine (DA) release and DA receptor sensitivity. Using two different animal models we show inhibition of dopaminergic activity in vivo by intracerebral PLA(2) application. (1) Unilateral stereotaxic injection of PLA(2) into the substantia nigra pars compacta causes an apomorphine-induced ipsilateral rotational asymmetry. (2) Intracerebroventricular PLA(2) application reduces apomorphine-induced locomotion. NMR spectroscopy studies show a disordered phospholipid metabolism in the prefrontal cortex (PFC) of schizophrenics. The hypofrontality hypothesis of schizophrenia postulates hypodopaminergic activity in the prefrontal cortex. We speculate that increased PLA(2) activity in the PFC of schizophrenics might be related to both abnormalities and could thus contribute to hypofrontality in schizophrenia.