Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phospholipase A2 (PLA2) is a key enzyme in the metabolism of phospholipids. Because a disordered phospholipid metabolism has frequently been reported in schizophrenia, we investigated the PLA2 activity in serum from 14 drug-free paranoid schizophrenic patients, 20 healthy controls, and 8 nonschizophrenic psychiatric patients. Schizophrenics showed significantly higher PLA2 activity than healthy controls and nonschizophrenic patients. The increment in schizophrenics was not due to increased concentration of pancreatic secretory PLA2, as concerning pancreatic PLA2 no differences were found among the 3 proband groups. The present findings confirm the results of our previous study and suggest that increased serum PLA2 activity might reflect an increment in the intracellular enzyme activity in schizophrenia. In the brain the activation of intracellular PLA2 results in changes in neuronal activity due to alterations in receptor sensitivity and in neurotransmitter metabolism. The possibility that such PLA2-induced mechanisms are involved in the pathogenesis of schizophrenia should be investigated in further experiments.
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PMID:Increased serum phospholipase A2 activity in schizophrenia: a replication study. 222 19

Phospholipase A2 (PLA2) is a key enzyme in the metabolism of phospholipids. PLA2 is enriched in neuronal membranes and plays an essential role in the functioning of membrane structures in the brain. Because a disordered phospholipid metabolism has been postulated in schizophrenia we started in 1985 a series of exploratory studies in an attempt to clarify the role of PLA2 in schizophrenic disorders. Our results can presently be summed up as follows: 1. Drug-free schizophrenics showed significantly higher PLA2 activity in serum and in plasma as compared with healthy controls as well as with nonschizophrenic psychiatric patients; the latter did not differ from the control group with regard to PLA2 activity. These findings suggest that increased PLA2 activity might be specific for schizophrenia. 2. The possibility that increased PLA2 activity is an artifact due to prior neuroleptic treatment could be ruled out as improbable by the findings that a) neuroleptic treatment significantly reduced PLA2 activity, and b) increased PLA2 activity was also found in first-onset, never-treated schizophrenic patients. 3. Increased PLA2 activity in schizophrenic patients was not caused by the entry of pancreatic enzyme into circulation. Our findings in serum rather suggest that the increment reflects increased intracellular enzyme activity. We speculate that our results might reflect an increment of the intraneuronal PLA2 activity in the brain. The activation of PLA2 in the brain was found to result in changes in neuronal function due to alterations in receptor sensitivity as well as in neurotransmitter metabolism. The possibility that such PLA2-induced mechanisms are involved in the pathology of schizophrenia should be investigated in further experiments.
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PMID:[Possible involvement of phospholipase A2 in the pathogenesis of schizophrenia]. 235 35

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)
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PMID:[Accelerated breakdown of membrane phospholipids in schizophrenia--implications for the hypofrontality hypothesis]. 783 20

Phospholipase A2 (PLA2) is a key enzyme in phospholipid metabolism. In neurons, membrane-bound PLA2 plays an essential role in signal transduction by affecting neurotransmitter release and receptor sensitivity. There are some reports of increased PLA2 activity in schizophrenia. We investigated the effects of intracerebroventricular (i.c.v.) injections of PLA2 on dopamine-mediated behavior in rats. Ten days after i.c.v. injection, PLA2 significantly inhibited apomorphine-induced locomotion as compared with i.c.v. saline injections. The inhibition of apomorphine-induced locomotion by PLA2 was reversible within 4 weeks after stereotaxic surgery. These findings suggest a functional inhibition of dopaminergic postsynaptic receptors by PLA2. Accelerated phospholipid metabolism and reduced dopaminergic activity in the prefrontal cortex have been postulated to play a role in schizophrenia. Increased PLA2 activity may be related to both abnormalities and could thus play a role in the pathophysiology of schizophrenia.
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PMID:Intracerebroventricular injection of phospholipase A2 inhibits apomorphine-induced locomotion in rats. 857 Jul 69

Phospholipase A2 (PLA2) is a key enzyme in the phospholipid metabolism. In the CNS intracellular PLA2 plays an essential role in signal transduction by affecting both dopamine (DA) release and DA-receptor sensitivity. In schizophrenia a disordered phospholipid metabolism and increased activity of PLA2 have been reported. In this study we investigated the effects of intracerebral PLA2 injections on dopaminergic neurotransmission in rats using Ungerstedt's model of rotational behavior. Circling behavior induced by the DA agonist apomorphine after unilateral PLA2 injections into the substantia nigra pars compacta was recorded. Seven and 21 days after intranigral PLA2 injection, apomorphine induced an ipsilateral rotation indicating a long-lasting inhibition of ipsilateral nigrostriatal dopaminergic pathway by PLA2 application. In schizophrenia a reduced dopaminergic activity in the frontal cortex has been hypothesized. Recent spectroscopy studies reported on an accelerated break-down of membrane phospholipids in the frontal cortex from schizophrenics. The present findings suggest that increased PLA2 activity in schizophrenia could accelerate the breakdown of membrane phospholipids and thus contribute to a hypodopaminergy in the frontal cortex of schizophrenic patients.
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PMID:Intracerebral injection of phospholipase A2 inhibits dopamine-mediated behavior in rats: possible implications for schizophrenia. 877 14

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.
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PMID:Phospholipase A2 and the hypofrontality hypothesis of schizophrenia. 888 32

Phospholipase A(2) (PLA2) is a key enzyme of the phospholipid metabolism which shows alteration in schizophrenia. Eye movement disturbances occur in a majority of patients with schizophrenia and in a proportion of their first-degree relatives, and they have been suggested as an endophenotypic marker in genetic studies of this illness. Here we report an association between the BAN I polymorphism of the cytosolic PLA2 gene (single nucleotide polymorphism in the first intron of the gene) and the intensity of eye movement disturbances (fixation and smooth pursuit) observed in 126 schizophrenic patients. The mean intensity of both kinds of eye movement disturbances was significantly higher in individuals homozygous for the A2 genotype compared with the remaining phenotypes. There was also a trend for greater A2 allele frequency in schizophrenic patients with a higher degree of eye movement disturbances. The relative frequency of the A2/A2 genotype was higher in patients with a greater degree of eye movement disturbances occurring during both fixation and smooth pursuit tests. Our results correspond to the other studies showing an association between the cPLA2 polymorphism and schizophrenia (predominance of the A2 allele in schizophrenic subjects).
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PMID:The study of cytosolic phospholipase A2 gene polymorphism in schizophrenia using eye movement disturbances as an endophenotypic marker. 1275 52