[Accelerated breakdown of membrane phospholipids in schizophrenia--implications for the hypofrontality hypothesis].
Phospholipase A2 (PLA2) is a key enzyme in the metabolism of membrane phospholipids. We and other authors (Noponen et al., 1993) reported on increased PLA2 activity in serum and plasma from schizophrenic patients as compared to healthy and psychiatric controls. This increment in PLA2 activity could be inhibited by neuroleptic therapy. The breakdown of membrane phospholipids by PLA2 produces cytotoxic products such as lysophosphatidylcholine (LPC). We found in an independent series of studies increased PLA2 activity, decreased membrane phospholipids and increased LPC concentrations in platelets from schizophrenics, suggesting an accelerated breakdown of membrane phospholipids in the disease. To clarify the effects of PLA2 in the brain we investigated the effects of intracerebral PLA2 injections on dopaminergic neurotransmission in rats using Ungerstedt's model of rotational behaviour. Circing behaviour induced by DA agonists after unilateral PLA2 injections into the substantia nigra pars compacta were recorded. One, three and five weeks after intranigral PLA2 injection apomorphine induced an ipsilateral rotation, indicating a long lasting inhibition of ipsilateral nigrostriatal dopaminergic pathway by PLA2 application. Taken together, our findings indicate that a) at least a subgroup of schizophrenic patients shows increased PLA2 activity and consequently an accelerated breakdown of platelet membrane phospholipids, and b) in animal experiments the intranigral application of PLA2 inhibited the dopaminergic activity. How could these findings be related to the biology of schizophrenia? In schizophrenia a reduced dopaminergic activity in the frontal cortex has been hypothesized. Recent spectroscopy studies reported on an accelerated breakdown of membrane phospholipids in the frontal cortex from schizophrenics.(ABSTRACT TRUNCATED AT 250 WORDS)
Gattaz
W F
WF
Arbeitsgruppe Neurobiologie, Zentralinstitut für Seelische Gesundheit Mannheim.
Brunner
J
J
Schmitt
A
A
Maras
A
A
D000328:Adult; D000818:Animals; D001792:Blood Platelets / Q000201:enzymology; D004292:Dominance, Cerebral / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000502:physiology*; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects / Q000503:physiopathology*; D006220:Haloperidol / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism*; D008875:Middle Aged; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000502:physiology; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012559:Schizophrenia / Q000188:drug therapy / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology; D013378:Substantia Nigra / Q000187:drug effects / Q000503:physiopathology
D008563:Membrane Lipids; D010743:Phospholipids; D010741:Phospholipases A; D054467:Phospholipases A2; D006220:Haloperidol; D004298:Dopamine
Beschleunigter Abbau von Membranphospholipiden bei der Schizophrenie--Implikationen für die Hypofrontalitätshypothese.