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Phospholipid metabolism in neuropsychiatric disorders

Grant number: 02/13633-7
Support Opportunities:Research Projects - Thematic Grants
Duration: December 01, 2003 - February 29, 2008
Field of knowledge:Health Sciences - Medicine - Psychiatry
Principal Investigator:Wagner Farid Gattaz
Grantee:Wagner Farid Gattaz
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Pesquisadores principais:
Emmanuel Dias-Neto
Associated grant(s):06/54743-0 - Interindividual variability in EEG correlates of attention and limits of functional mapping, AR.EXT
Associated scholarship(s):07/05207-1 - Proteome analysis of schizophrenia human brain tissue from posterior superior temporal gyrus, BP.PD
05/52897-8 - Learning effects on phospholipase A2 activity and membrane fluidity in the associative parietal cortex of rats, BP.IC
05/52898-4 - Phospholipase A2 inhibition in the hippocampus of mice and their differential effects on the free flow of plasma and nuclear membranes: are there any possible correlations with memory?, BP.IC
+ associated scholarships 05/52899-0 - Phospholipase A2 inhibition in the hippocampus of mice and their differential effects on the free flow of plasma and nuclear membranes: are there any possible correlations with memory?, BP.IC
05/52896-1 - Learning effects on phospholipase A2 activity and the free flow of membranes in the prefrontal cortex of rats, BP.IC
04/02165-8 - Dynamics of gene expression of phospholipase A2 and the amyloid precursor protein (APP) in the brain: implications for memory and Alzheimer's Disease, BP.DD
04/08890-6 - Stimulation of phospholipase A2 in the hippocampus of rats and its effects on memory: therapeutic implications for Alzheimer's Disease, BP.PD - associated scholarships


The physicochemical properties of the neuronal membrane have a major impact on neural cell metabolism, affecting brain function and plasticity. As a continuation of former and recent work on this field, the primary objective of this project is to investigate the membrane phospholipid metabolism in three neuropsychiatric diseases, namely schizophrenia, Alzheimer's disease (AD) and temporal lobe epilepsy. We are particularly interested on the neurobiology of phospholipase A2 (PLA2), the main phospholipid-cleaving enzyme in neurons, and its effects on the composition and properties of the neuronal membrane. Previous data from our group and others have consistently shown that PLA2 activity is increased in schizophrenics, and reduced in AD. Such abnormality, which can be further detected in peripheral blood platelets, correlate with discrete clinical and pathological findings. In schizophrenia, increased PLA2 activity was shown to be associated with negative symptoms, suggesting greater frontal lobe dysfunction. In platelet membranes of schizophrenics, PLA2 hyperactivity (and abnormal precursor and metabolite levels) was reverted after neuroleptic treatment. In AD post-mortem brains, lower cerebral PLA2 levels were correlated with higher counts of senile plaques and neurofibrillary tangles. Lower platelet PLA2 activity was further correlated with the severity of cognitive decline in AD, and predicted a more deteriorating outcome. Likewise, abnormal in vivo cerebral phospholipid turnover, as detected by 31P-spectroscopy scans, was associated with a worse performance on neuropsychological tests in AD. We propose a multidisciplinary project in order to investigate the genetic determinants and biological modulators of membrane phospholipid metabolism, addressing the clinical neurobiology of three major neuropsychiatric disorders. The genetic and biochemical regulation of phospholipid metabolism will be addressed in vitro and in vivo with the aid of laboratory techniques, primary neuronal cultures, and animal models. Biological samples obtained from patients in each group will be evaluated in the light of the respective clinical findings, focusing on psychopathology, cognitive neuropsycology, electrophysiology, and functional neuroimaging... (AU)

Articles published in Pesquisa FAPESP Magazine about the research grant:
Falta de armonía celular 
Cellular disharmony 
A jigsaw puzzle in construction 
Articles published in Agência FAPESP Newsletter about the research grant:
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Scientific publications (20)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
RENATO ANGHINAH; PAULO AFONSO MEDEIROS KANDA; HELDER FREDERICO LOPES; LUIS FERNANDO HINDI BASILE; SÉRGIO MACHADO; PEDRO RIBEIRO; BRUNA VELASQUES; KOICHI SAMESHIMA; DANIEL YASUMASA TAKAHASHI; LÉCIO FIGUEIRA PINTO; et al. EEGq na doença de Alzheimer: análise espectral versus coerência. O que é melhor?. Arquivos de Neuro-Psiquiatria, v. 69, n. 6, p. 871-874, . (02/13633-7)
LUIS F. H. BASILE. Complex, multifocal, individual-specific attention-related cortical functional circuits. Biological Research, v. 40, n. 4, p. 451-470, . (02/13633-7)
CRISPIM NASCIMENTO, CARLA MANUELA; PEREIRA, JESSICA RODRIGUES; DE ANDRADE, LARISSA PIRES; GARUFFI, MARCELO; AYAN, CARLOS; KERR, DANIEL SHIKANAI; TALIB, LEDA LEME; COMINETTI, MARCIA REGINA; STELLA, FLORINDO. Physical Exercise Improves Peripheral BDNF Levels and Cognitive Functions in Mild Cognitive Impairment Elderly with Different BDNF Val66Met Genotypes. JOURNAL OF ALZHEIMER'S DISEASE, v. 43, n. 1, p. 81-91, . (02/13633-7)
APRAHAMIAN, IVAN; SANTOS, FRANKLIN S.; DOS SANTOS, BERNARDO; TALIB, LEDA; DINIZ, BRENO S.; RADANOVIC, MARCIA; GATTAZ, WAGNER F.; FORLENZA, ORESTES V.. Long-Term, Low-Dose Lithium Treatment Does Not Impair Renal Function in the Elderly: A 2-Year Randomized, Placebo-Controlled Trial Followed by Single-Blind Extension. JOURNAL OF CLINICAL PSYCHIATRY, v. 75, n. 7, p. E672-E678, . (02/13633-7)
SCHAEFFER, EVELIN L.; SKAF, HENI D.; NOVAES, BARBARA DE A.; DA SILVA, EMANUELLE R.; MARTINS, BEATRIZ A.; JOAQUIM, HENRIQUE D. G.; GATTAZ, WAGNER F.. Inhibition of phospholipase A(2) in rat brain modifies different membrane fluidity parameters in opposite ways. PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, v. 35, n. 7, p. 1612-1617, . (05/52899-0, 05/52898-4, 04/14516-0, 02/13633-7, 08/09861-0, 08/09494-8)
FORLENZA, ORESTES V.; TORRES, CAROLINA A.; TALIB, LEDA L.; DE PAULA, VANESSA J.; JOAQUIM, HELENA P. G.; DINIZ, BRENO S.; GATTAZ, WAGNER F.. Increased platelet GSK3B activity in patients with mild cognitive impairment and Alzheimer's disease. JOURNAL OF PSYCHIATRIC RESEARCH, v. 45, n. 2, p. 220-224, . (02/13633-7)
ANGHINAH, RENATO; MEDEIROS KANDA, PAULO AFONSO; LOPES, HELDER FREDERICO; HINDI BASILE, LUIS FERNANDO; MACHADO, SERGIO; RIBEIRO, PEDRO.; VELASQUES, BRUNA; SAMESHIMA, KOICHI; TAKAHASHI, DANIEL YASUMASA; PINTO, LECIO FIGUEIRA; et al. Alzheimer's disease qEEG Spectral analysis versus coherence. Which is the best measurement?. Arquivos de Neuro-Psiquiatria, v. 69, n. 6, p. 871-874, . (02/13633-7)
TALIB, L. L.; HOTOTIAN, S. R.; JOAQUIM, H. P. G.; FORLENZA, O. V.; GATTAZ, W. F.. Increased iPLA2 activity and levels of phosphorylated GSK3B in platelets are associated with donepezil treatment in Alzheimer's disease patients. EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE, v. 265, n. 8, p. 701-706, . (02/13633-7, 09/52825-8)
DE-PAULA, VANESSA J.; SCHAEFFER, EVELIN L.; TALIB, LEDA L.; GATTAZ, WAGNER F.; FORLENZA, ORESTES V.. Inhibition of phospholipase A(2) increases Tau phosphorylation at Ser214 in embryonic rat hippocampal neurons. PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS, v. 82, n. 1, p. 57-60, . (02/13633-7)
FORLENZA, ORESTES V.; DINIZ, BRENO S.; RADANOVIC, MARCIA; SANTOS, FRANKLIN S.; TALIB, LEDA L.; GATTAZ, WAGNER F.. Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial. BRITISH JOURNAL OF PSYCHIATRY, v. 198, n. 5, p. 351-356, . (02/13633-7)
SCHAEFFER, EVELIN L.; DE-PAULA, VANESSA J.; DA SILVA, EMANUELLE R.; NOVAES, BARBARA DE A.; SKAF, HENI D.; FORLENZA, ORESTES V.; GATTAZ, WAGNER F.. Inhibition of phospholipase A(2) in rat brain decreases the levels of total Tau protein. JOURNAL OF NEURAL TRANSMISSION, v. 118, n. 9, p. 1273-1279, . (04/14516-0, 02/13633-7, 08/09861-0, 08/09494-8)
DINIZ, BRENO S.; NUNES, PAULA V.; MACHADO-VIEIRA, RODRIGO; FORLENZA, ORESTES V.. Current pharmacological approaches and perspectives in the treatment of geriatric mood disorders. CURRENT OPINION IN PSYCHIATRY, v. 24, n. 6, p. 473-477, . (02/13633-7)
APRAHAMIAN, IVAN; NUNES, PAULA V.; FORLENZA, ORESTES V.. Cognitive impairment and dementia in late-life bipolar disorder. CURRENT OPINION IN PSYCHIATRY, v. 26, n. 1, p. 120-123, . (02/13633-7)
FORLENZA, ORESTES V.; DINIZ, BRENO S.; GATTAZ, WAGNER F.. Diagnosis and biomarkers of predementia in Alzheimer's disease. BMC MEDICINE, v. 8, . (02/13633-7)
FORLENZA‚ O.V.; WACKER‚ P.; NUNES‚ P.V.; YACUBIAN‚ J.; CASTRO‚ C.C.; OTADUY‚ M.C.G.; GATTAZ‚ W.F.. Reduced phospholipid breakdown in Alzheimer’s brains: a 31 P spectroscopy study. Psychopharmacology, v. 180, n. 2, p. 359-365, . (97/11083-0, 02/13633-7, 99/00740-5)
FLAKS‚ M.K.; YASSUDA‚ M.S.; REGINA‚ A.C.B.; CID‚ C.G.; CAMARGO‚ C.H.P.; GATTAZ‚ W.F.; FORLENZA‚ O.V.. The Short Cognitive Performance Test (SKT): a preliminary study of its psychometric properties in Brazil. INTERNATIONAL PSYCHOGERIATRICS, v. 18, n. 1, p. 121-134, . (02/13633-7)
ZAINAGHI‚ I.A.; FORLENZA‚ O.V.; GATTAZ‚ W.F.. Abnormal APP processing in platelets of patients with Alzheimer’s disease: correlations with membrane fluidity and cognitive decline. Psychopharmacology, v. 192, n. 4, p. 547-553, . (02/13633-7)
DE-PAULA, VANESSA J.; KERR, DANIEL S.; SCOLA, GUSTAVO; GATTAZ, WAGNER F.; FORLENZA, ORESTES V.. Lithium Distinctly Modulates the Secretion of Pro- and Anti-Inflammatory Interleukins in Co-Cultures of Neurons and Glial Cells at Therapeutic and Sub-Therapeutic Concentrations. Current Alzheimer Research, v. 13, n. 8, p. 848-852, . (13/01352-8, 11/19892-3, 02/13633-7)
NASCIMENTO, CARLA MANUELA CRISPIM; PEREIRA, JESSICA RODRIGUES; DE ANDRADE, LARISSA PIRES; GARUFFI, MARCELO; TALIB, LEDA LEME; FORLENZA, ORESTES VICENTE; MARIA CANCELA, JOSE; COMINETTI, MARCIA REGINA; STELLA, FLORINDO. Physical Exercise in MCI Elderly Promotes Reduction of Pro-Inflammatory Cytokines and Improvements on Cognition and BDNF Peripheral Levels. Current Alzheimer Research, v. 11, n. 8, p. 799-805, . (02/13633-7)
TALIB, LEDA L.; JOAQUIM, HELENA P. G.; FORLENZA, ORESTES V.. Platelet biomarkers in Alzheimer's disease. WORLD JOURNAL OF PSYCHIATRY, v. 2, n. 6, p. 7-pg., . (02/13633-7)

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