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Phospholipid metabolism in neuropsychiatric disorders

Grant number: 02/13633-7
Support type:Research Projects - Thematic Grants
Duration: December 01, 2003 - February 29, 2008
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Wagner Farid Gattaz
Grantee:Wagner Farid Gattaz
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Co-Principal Investigators: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
05/52899-0 - 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
+ associated scholarships 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
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

Abstract

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:
Cellular disharmony 
A jigsaw puzzle in construction 

Scientific publications (19)
(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)
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, 2016. Web of Science Citations: 6.
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, DEC 2015. Web of Science Citations: 12.
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, 2015. Web of Science Citations: 47.
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, JUL 2014. Web of Science Citations: 34.
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, 2014. Web of Science Citations: 62.
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, JAN 2013. Web of Science Citations: 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; CARAMELLI, PAULO; NITRINI, RICARDO. Alzheimer's disease qEEG Spectral analysis versus coherence. Which is the best measurement?. Arquivos de Neuro-Psiquiatria, v. 69, n. 6, p. 871-874, DEC 2011. Web of Science Citations: 9.
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, NOV 2011. Web of Science Citations: 6.
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, SEP 2011. Web of Science Citations: 15.
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, AUG 15 2011. Web of Science Citations: 12.
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, MAY 2011. Web of Science Citations: 189.
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, FEB 2011. Web of Science Citations: 57.
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; PAULO CARAMELLI; RICARDO NITRINI. Alzheimer's disease qEEG: spectral analysis versus coherence. which is the best measurement?. Arquivos de Neuro-Psiquiatria, v. 69, n. 6, p. -, Dez. 2011.
FORLENZA, ORESTES V.; DINIZ, BRENO S.; GATTAZ, WAGNER F. Diagnosis and biomarkers of predementia in Alzheimer's disease. BMC MEDICINE, v. 8, DEC 22 2010. Web of Science Citations: 68.
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, JAN 2010. Web of Science Citations: 10.
LUIS F. H. BASILE. Complex, multifocal, individual-specific attention-related cortical functional circuits. Biological Research, v. 40, n. 4, p. 451-470, 2007.
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, 2007.
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, 2006.
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, 2005.

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