DANIEL SHIKANAI KERR
Projetos de Pesquisa
Unidades Organizacionais
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
6 resultados
Resultados de Busca
Agora exibindo 1 - 6 de 6
- The Absence of CYP3A5*3 Is a Protective Factor to Anticonvulsants Hypersensitivity Reactions: A Case-Control Study in Brazilian Subjects (vol 10, e0136141, 2015)(2015) TANNO, Luciana Kase; KERR, Daniel Shikanai; SANTOS, Bernardo dos; TALIB, Leda Leme; YAMAGUTI, Celia; RODRIGUES, Helcio; GATTAZ, Wagner Farid; KALIL, Jorge
- Chronic Lithium Treatment Increases Telomere Length in Parietal Cortex and Hippocampus of Triple-Transgenic Alzheimer's Disease Mice(2018) CARDILLO, Giancarlo de Mattos; DE-PAULA, Vanessa de Jesus Rodrigues; IKENAGA, Eliza Hiromi; COSTA, Luciana Rodrigues; CATANOZI, Sergio; SCHAEFFER, Evelin Lisete; GATTAZ, Wagner Farid; KERR, Daniel Shikanai; FORLENZA, Orestes VicenteTelomere length (TL) is a biomarker of cell aging, and its shortening has been linked to several age-related diseases. In Alzheimer's disease (AD), telomere shortening has been associated with neuroinflammation and oxidative stress. The majority of studies on TL in AD were based on leucocyte DNA, with little information about its status in the central nervous system. In addition to other neuroprotective effects, lithium has been implicated in the maintenance of TL. The present study aims to determine the effect of chronic lithium treatment on TL in different regions of the mouse brain, using a triple-transgenic mouse model (3xTg-AD). Eighteen transgenic and 22 wild-type (Wt) male mice were treated for eight months with chow containing 1.0 g (Li1) or 2.0 g (Li2) of lithium carbonate/kg, or standard chow (Li0). DNA was extracted from parietal cortex, hippocampus and olfactory epithelium and TL was quantified by real-time PCR. Chronic lithium treatment was associated with longer telomeres in the hippocampus (Li2, p = 0.0159) and in the parietal cortex (Li1, p = 0.0375) of 3xTg-AD compared to Wt. Our findings suggest that chronic lithium treatment does affect telomere maintenance, but the magnitude and nature of this effect depend on the working concentrations of lithium and characteristics of the tissue. This effect was observed when comparing 3xTg-AD with Wt mice, suggesting that the presence of AD pathology was required for the lithium modulation of TL.
- Antipsychotic drugs decrease iPLA(2) gene expression in schizophrenia(2013) KERR, Daniel Shikanai; TALIB, Leda Leme; YAMAMOTO, Victor Junji; FERREIRA, Aline S.; ZANETTI, Marcus V.; SERPA, Mauricio H.; BUSATTO, Geraldo F.; BILT, Martinus Theodorus Van de; GATTAZ, Wagner Farid
- COMT Met (158) modulates facial emotion recognition in bipolar I disorder mood episodes(2012) SOEIRO-DE-SOUZA, Marcio Gerhardt; BIO, Danielle Soares; DAVID, Denise Petresco; SANTOS JR., Domingos Rodrigues dos; KERR, Daniel Shikanai; GATTAZ, Wagner Farid; MACHADO-VIEIRA, Rodrigo; MORENO, Ricardo AlbetoBackground: One of the many cognitive deficits reported in bipolar disorder (BD) patients is facial emotion recognition (FER), which has recently been associated with dopaminergic catabolism. Catechol-O-methyltransferase (COMT) is one of the main enzymes involved in the metabolic degradation of dopamine (DA) in the prefrontal cortex (PFC). The COMT gene polymorphism rs4680 (Val(158)Met) Met allele is associated with decreased activity of this enzyme in healthy controls. The objective of this study was to evaluate the influence of Val(158)Met on FER during manic and depressive episodes in BD patients and in healthy controls. Materials and methods: 64 BD type I patients (39 in manic and 25 in depressive episodes) and 75 healthy controls were genotyped for COMT rs4680 and assessed for FER using the Ekman 60 Faces (EK60) and Emotion Hexagon (Hx) tests. Results: Bipolar manic patients carrying the Met allele recognized fewer surprised faces, while depressed patients with the Met allele recognized fewer ""angry"" and ""happy"" faces. Healthy homozygous subjects with the Met allele had higher FER scores on the Hx total score, as well as on ""disgust"" and ""angry"" faces than other genotypes. Conclusion: This is the first study suggesting that COMT rs4680 modulates FER differently during BD episodes and in healthy controls. This provides evidence that PFC DA is part of the neurobiological mechanisms of social cognition. Further studies on other COMT polymorphisms that include euthymic BD patients are warranted. ClinicalTrials.gov Identifier: NCT00969.
- Long-Term Lithium Treatment Increases cPLA(2) and iPLA(2) Activity in Cultured Cortical and Hippocampal Neurons(2015) DE-PAULA, Vanessa de Jesus; KERR, Daniel Shikanai; CARVALHO, Marilia Palma Fabiano de; SCHAEFFER, Evelin Lisete; TALIB, Leda Leme; GATTAZ, Wagner Farid; FORLENZA, Orestes VicenteBackground: Experimental evidence supports the neuroprotective properties of lithium, with implications for the treatment and prevention of dementia and other neurodegenerative disorders. Lithium modulates critical intracellular pathways related to neurotrophic support, inflammatory response, autophagy and apoptosis. There is additional evidence indicating that lithium may also affect membrane homeostasis. Objective: To investigate the effect of lithium on cytosolic phospholipase A(2) (PLA(2)) activity, a key player on membrane phospholipid turnover which has been found to be reduced in blood and brain tissue of patients with Alzheimer's disease (AD). Methods: Primary cultures of cortical and hippocampal neurons were treated for 7 days with different concentrations of lithium chloride (0.02 mM, 0.2 mM and 2 mM). A radio-enzymatic assay was used to determine the total activity of PLA(2) and two PLA(2) subtypes: cytosolic calcium-dependent (cPLA(2)); and calcium-independent (iPLA(2)). Results: cPLA(2) activity increased by 82% (0.02 mM; p = 0.05) and 26% (0.2 mM; p = 0.04) in cortical neurons and by 61% (0.2 mM; p = 0.03) and 57% (2 mM; p = 0.04) in hippocampal neurons. iPLA(2) activity was increased by 7% (0.2 mM; p = 0.04) and 13% (2 mM; p = 0.05) in cortical neurons and by 141% (0.02 mM; p = 0.0198) in hippocampal neurons. Conclusion: long-term lithium treatment increases membrane phospholipid metabolism in neurons through the activation of total, c- and iPLA(2). This effect is more prominent at sub-therapeutic concentrations of lithium, and the activation of distinct cytosolic PLA(2) subtypes is tissue specific, i.e., iPLA(2) in hippocampal neurons, and cPLA(2) in cortical neurons. Because PLA(2) activities are reported to be reduced in Alzheimer's disease (AD) and bipolar disorder (BD), the present findings provide a possible mechanism by which long-term lithium treatment may be useful in the prevention of the disease.
- The Absence of CYP3A5*3 Is a Protective Factor to Anticonvulsants Hypersensitivity Reactions: A Case-Control Study in Brazilian Subjects(2015) TANNO, Luciana Kase; KERR, Daniel Shikanai; SANTOS, Bernardo dos; TALIB, Leda Leme; YAMAGUTI, Celia; RODRIGUES, Helcio; GATTAZ, Wagner Farid; KALIL, JorgeAlthough aromatic anticonvulsants are usually well tolerated, they can cause cutaneous adverse drug reactions in up to 10% of patients. The clinical manifestations of the antiepileptics-induced hypersensitivity reactions (AHR) vary from mild skin rashes to severe cutaneous drug adverse reactions which are related to high mortality and significant morbidity. Genetic polymorphisms in cytochrome P450 genes are associated with altered enzymatic activity and may contribute to the risk of AHR. Here we present a case-control study in which we genotyped SNPs of CYP2C19, 2C9 and 3A5 of 55 individuals with varying severities of AHR, 83 tolerant, and 366 healthy control subjects from Sao Paulo, Brazil. Clinical characterization was based on standardized scoring systems and drug patch test. All in vivo investigation followed the ENDA (European Network of Drug Allergy) recommendations. Genotype was determined by real time PCR using peripheral blood DNA as a template. Of all 504 subjects, 65% were females, 45% self-identified as Afro-American, 38% as Caucasian and 17% as having non-African mixed ascendancy. Amongst 55 subjects with AHR, 44 had severe cutaneous drug adverse reactions. Of the 46 drug patch tests performed, 29 (63%) were positive. We found a strong association between the absence of CYP3A5*3 and tolerant subjects when compared to AHR (p = 0.0002, OR = 5.28 [CI95% 2.09-14.84]). None of our groups presented positive association with CYP2C19 and 2C9 polymorphisms, however, both SNPs contributed to separation of cases and tolerants in a Classification and Regression Tree. Our findings indicate that drug metabolism genes can contribute in the tolerability of antiepileptics. CYP3A5*3 is the most prevalent CYP3A5 allele associated with reduced enzymatic function. The current study provides evidence that normal CYP3A5 activity might be a protective factor to aromatic antiepileptics-induced hypersensitivity reactions in Brazilian subjects.