Phospholipase A2 and the hypofrontality hypothesis of schizophrenia.
Phospholipase A2 (PLA2) catalyzes the hydrolysis of membrane phospholipids to release cytotoxic products such as lysophosphatidylcholine. In schizophrenia increased PLA2 activity and an accelerated breakdown of membrane phospholipids have been reported. In neuronal do membranes PLA2 modulates dopamine (DA) release and DA receptor sensitivity. Using two different animal models we show inhibition of dopaminergic activity in vivo by intracerebral PLA2 application. (1) Unilateral stereotaxic injection of PLA2 into the substantia nigra pars compacta causes an apomorphine-induced ipsilateral rotational asymmetry. (2) Intracerebroventricular PLA2 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 PLA2 activity in the PFC of schizophrenics might be related to both abnormalities and could thus contribute to hypofrontality in schizophrenia.
Neurobiology Unit, Central Institute of Mental Health, Mannheim, Germany. gattaz@as200.zi-mannheim.de
W F
WF
Gattaz
J
J
Brunner
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D005260:Female; D007276:Injections, Intraventricular; D008297:Male; D010741:Phospholipases A / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism*; D054467:Phospholipases A2; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012559:Schizophrenia / Q000201:enzymology / Q000209:etiology*; D013378:Substantia Nigra
D018491:Dopamine Agonists; D010741:Phospholipases A; D054467:Phospholipases A2; D001058:Apomorphine