Increased phospholipase A2 activity in schizophrenia

Gattaz, Wagner F.; Ferber, E.; Pangerl, Andreas

doi:10.1016/0920-9964(92)90191-7

Cited by 48 publications

(77 citation statements)

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“…57 (d) Increased calcium-independent PLA2 activity has been replicated in both peripheral and CNS tissue, and in drug naïve patients (Table 1). 62,72,76,78 (e) Higher calcium-independent PLA2 activity correlates significantly with greater severity of psychopathology, suggesting a direct relationship between the degree of PLA2G6A activity and disease progression. 72 (f) Though numbers were small, the work of Tavares et al 62 supports the concept of antipsychotic efficacy through modulating PLA2 activity.…”

Section: Discussionmentioning

confidence: 99%

“…62,72,[75][76][77][78] Higher calcium-independent PLA2 activity has been correlated to greater severity of psychopathology 72 though other positive studies have not seen this association. 62,75 Katila et al 79 reported normal calcium-independent PLA2 activity in schizophrenia, though Lasch et al 77 suggest this may have been a methodological problem.…”

Section: Direct Evidence Of Altered Pla2 Activity In Schizophreniamentioning

confidence: 99%

“…62,75 Three positive studies, and one negative study measuring calcium-independent activity utilised a portion of drug naïve patients. 62,75,76,79 Statistical analysis has found no correlation between medication state and calcium-dependent PLA2 activity. 64,72,80 A small population of drug naïve patients had normal calcium-dependent PLA2 activity.…”

Section: Calcium-dependent Pla2mentioning

confidence: 99%

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The role of phospholipases A2 in schizophrenia

Law¹,

Cotton²,

Berger

2006

Mol Psychiatry

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Direct Evidence Of Altered Pla2 Activity In Schizophreniamentioning

confidence: 99%

Section: Calcium-dependent Pla2mentioning

confidence: 99%

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The role of phospholipases A2 in schizophrenia

Law¹,

Cotton²,

Berger

2006

Mol Psychiatry

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“…Evidence of disturbed lipid metabolism in schizophrenia is based on a variety of findings, including altered cerebral phospholipids (Fukuzako, 2001;Keshavan et al, 2000;Stanley et al, 2000), upregulation of phospholipase A 2 (PLA 2 ) activity (Gattaz et al, 1987(Gattaz et al, , 1990(Gattaz et al, , 1995Ross et al, 1997;Smesny et al, 2005a), diminished arachidonic acid levels (Berger et al, 2002Fenton et al, 2000;Reddy et al, 2004;Reddy and Yao, 2003), and impaired function of bioactive lipids (eg prostaglandins) (Smesny, 2004b;Ward, 2000). Dysfunction of prostaglandin-mediated processesFmeasured as attenuation of niacin skin flushingFwas associated with cerebral lipid metabolites (Puri et al, 2006), increased PLA 2 activity (Tavares et al, 2003), and decreased arachidonic acid levels (Glen et al, 1996;Messamore, 2003) and was also reported in nonaffected parents of schizophrenia patients (Waldo, 1999).…”

Section: Introductionmentioning

confidence: 99%

Cannabinoids Influence Lipid–Arachidonic Acid Pathways in Schizophrenia

Smesny

Rosburg

Baur

et al. 2007

Neuropsychopharmacol

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Increasing evidence suggests modulating effects of cannabinoids on time of onset, severity, and outcome of schizophrenia. Efforts to discover the underlying pathomechanism have led to the assumption of gene Â environment interactions, including premorbid genetical vulnerability and worsening effects of continuing cannabis use. The objective of this cross-sectional study is to investigate the relationship between delta-9-tetrahydrocannabinol intake and niacin sensitivity in schizophrenia patients and healthy controls. Intensity of niacin skin flushing, indicating disturbed prostaglandin-mediated processes, was used as peripheral marker of lipid-arachidonic acid pathways and investigated in cannabis-consuming and nonconsuming schizophrenia patients and in healthy controls. Methylnicotinate was applied in three concentrations onto the forearm skin. Flush response was assessed in 3-min intervals over 15 min using optical reflection spectroscopy. In controls, skin flushing was significantly decreased in cannabis-consuming as compared to nonconsuming individuals. When comparing the nonconsuming subgroups, patients showed significantly decreased flush response. The populations as a whole (patients and controls) showed an inverse association between skin flushing and sum scores of Symptom Check List 90-R. Results demonstrate an impact of long-term cannabis use on lipid-arachidonic acid pathways. Considering pre-existing vulnerability of lipid metabolism in schizophrenia, observed effects of cannabis use support the notion of a gene Â environment interaction.

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“…15,20 Não encontramos qualquer diferença na concentração da PLA2 pancreática entre os três grupos. En-…”

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Neuroquímica da esquizofrenia: papel dos fosfolípides

Gattaz

2000

Rev. Bras. Psiquiatr.

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IntroduçãoNão se encontrou ainda uma alteração neuroquímica definitiva na esquizofrenia. Para a maioria de achados positivos descritos na literatura, encontram-se também estudos com resultados negativos. Em outra ocasião, já discutimos os potenciais aspectos metodológicas que vêm contribuindo para a inconsistência de resultados até o momento.1 Alguns resultados experimentais mais consistentes foram resumidos recentemente 2 e incluem alterações de receptores dopaminérgicos (D2-like) nos gânglios da base, de receptores serotoninérgicos (5-HT1A e 5HT2) no córtex frontal, assim como alterações nos sistemas gabaérgicos e glutamatérgicos.Se a esquizofrenia for considerada uma síndrome resultante de um distúrbio na maturação do cérebro, é provável que parte das alterações neuroquímicas descritas sejam secundárias à alteração básica da plasticidade cerebral durante a infância e a adolescência. Isso implica dirigir a procura de fatores causais e primários dentre os processos biológicos que modulam a maturação cerebral. Nesse sentido, a evidência experimental acumulada na última década sugere que um distúrbio no metabolismo dos fosfolípides seja um candidato ao papel de fator primário na biologia da esquizofrenia. Metabolismo dos fosfolípides e função cerebralProcessos do metabolismo da membrana neuronal influenciam de forma decisiva a plasticidade e a função do cérebro. A camada dupla de fosfolipídeos que compõe a membrana neuronal determina as suas propriedades físico-químicas. Assim, a estrutura da membrana determina a sua fluidez, influencia o número e a afinidade dos receptores nela ligados, e modula os processos de transdução de sinais. Os fosfolípides são os principais componentes da membrana neuronal. Eles servem também como substrato para a síntese de mediadores intra e extracelulares, aumentando, assim, sua relevância para a neurotransmissão. 3O metabolismo dos fosfolípides é controlado por enzimas ligadas à membrana. A enzima fosfolipase A2 (PLA2) tem aqui uma função primordial. A PLA2 catalisa nos fosfolipídeos a hidrólise de ácidos graxos ligados à posição sn-2, liberando da membrana ácidos graxos livres e lisofosfolípides. Tanto o ácido araquidônico livre e as prostaglandinas que deles resultam, como a lisofosfatidilcolina, são importantes mediadores na transmissão e no processamento de sinais neuronais. 4 Assim, alterações na atividade da PLA2 podem ser relevantes para o surgimento e para o curso de diferentes doenças neuropsiquiátricas. De fato, distúrbios da PLA2 já foram descritos em pacientes com esclerose múltipla e com epilepsia do lobo temporal. 5,6 Distúrbio do metabolismo de fosfolípides na esquizofreniaDiversos estudos in vivo e post mortem encontraram um distúrbio do metabolismo de fosfolípides no cérebro de pacientes esquizofrênicos. Estudos com 31P-espectroscopia magnética sugerem uma aceleração do metabolismo de fosfolipídeos no lobo frontal de esquizofrênicos. Nesses estudos investigaramse as ressonâncias dos fosfomonoesterase (PME) e dos fosfodiesterase (PDE), respectivamente, os precursores...

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Increased phospholipase A2 activity in schizophrenia

Cited by 48 publications

References 0 publications

The role of phospholipases A2 in schizophrenia

The role of phospholipases A2 in schizophrenia

Cannabinoids Influence Lipid–Arachidonic Acid Pathways in Schizophrenia

Neuroquímica da esquizofrenia: papel dos fosfolípides

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