DANIEL SHIKANAI KERR
Projetos de Pesquisa
Unidades Organizacionais
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
5 resultados
Resultados de Busca
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- Association study of functional polymorphisms of dopaminergic pathway in epilepsy-related factors of temporal lobe epilepsy in Brazilian population(2018) ALCANTARA, J. A.; VINCENTIS, S.; KERR, D. S.; SANTOS, B. dos; ALESSI, R.; LINDEN JR., H. van der; CHAIM, T.; SERPA, M. H.; BUSATTO, G. F.; GATTAZ, W. F.; DEMARQUE, R.; VALENTE, K. D.Background and purposeThere are few data about the role of neurotransmission modulated by dopamine in epilepsy, especially temporal lobe epilepsy (TLE). This is the first study that aimed to analyze the dopaminergic polymorphisms in an etiologically homogeneous group of patients with TLE with hippocampal sclerosis. Selected polymorphisms were: (i) the most expressed D2-like receptors in the limbic system (DRD2/ANKK1 TAQ-1A, D4_VNTR and D4_rs1800955); (ii) the dopamine transporter (DAT) 3-untranslated region and intron 8; and (iii) two degrading enzymes regulating the synaptic activity, i.e. the main metabolizer of dopamine, catechol-O-methyltransferase, and monoamine oxidase A. MethodsWe assessed 119 patients with unequivocal TLE with hippocampal sclerosis and 112 healthy volunteers. Individuals were genotyped for the polymorphisms of the gene encoding dopaminergic pathway transporter DAT haplotype, dopaminergic receptors, catechol-O-methyltransferase and monoamine oxidase A. We also evaluated epilepsy-related factors (e.g. seizure frequency, age of onset, duration and status epilepticus). ResultsThere was no difference between the groups for the studied polymorphisms. The polymorphism DRD4_VNTR was associated with family history of epilepsy (P = 0.003), DRD2_rs1800497 was related to status epilepticus (P = 0.022), and intron 8 VNTR DAT was related to higher seizure frequency (P = 0.019) and family history of epilepsy (P = 0.011). ConclusionsOur findings demonstrated that polymorphisms of the dopaminergic pathway are associated with significant clinical features of this form of epilepsy, such as seizure frequency, family history of epilepsy and status epilepticus.
- Genetic polymorphisms of the 5HT receptors are not related with depression in temporal lobe epilepsy caused by hippocampal sclerosis(2018) VINCENTIIS, Silvia; ALCANTARA, Juliana; RZEZAK, Patricia; KERR, Daniel S.; GATTAZ, Wagner F.; LINDEN JR., Helio van der; SANTOS, Bernardo dos; MELO-SOUZA, Sebastiao E.; ARRUDA, Francisco; RAGAZZO, Paulo; CHAIM-AVANCINI, Tiffany; SERPA, Mauricio H.; FERNANDES, Fernando; MORENO, Ricardo A.; BUSATTO, Geraldo; ALESSI, Ruda; DEMARQUE, Renata; VALENTE, Kette D.Background: Temporal lobe epilepsy caused by hippocampal sclerosis (TLE-HS) is the most frequent form of drug-resistant epilepsy in adults. Mood disorders are the most frequent psychiatric comorbidities observed in these patients. Common pathophysiological mechanisms of epilepsy and psychiatric comorbidities include abnormalities in the serotonin pathway. The primary goal of this study was to determine the possible association between polymorphisms of genes encoding the serotonin receptors 5HT1A (rs6295), 5HT1B (rs6296), and 5HT2C (rs6318) and the presence of mood disorders in patients with TLE-HS. Our secondary goal was to evaluate the possible association between these variants and susceptibility to develop seizures in TLE-HS. Methods: We assessed 119 patients with TLE-HS, with and without psychiatric comorbidities; 146 patients with major depressive disorder; and 113 healthy volunteers. Individuals were genotyped for the rs6295, rs6296, and rs6318 polymorphisms. Results: No difference was observed between the group with TLE-HS, healthy controls, and the group with major depressive disorder without epilepsy regarding the polymorphisms that were evaluated. There was no correlation between rs6318, rs6295, rs6296, and epilepsy-related factors and history of psychiatric comorbidities. Conclusions: Our work suggests that the studied polymorphisms were not related to the presence of TLE, psychiatric comorbidities in TLE, and epilepsy-related factors.
- 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.
- BDNF Val66Met polymorphism is not related with temporal lobe epilepsy caused by hippocampal sclerosis in Brazilian population(2018) ALCANTARA, Juliana A.; VINCENTIIS, Silvia; SANTOS, Bernardo; KERR, Daniel; PAULA, Vanessa de; ALESSI, Ruda; LINDEN, Helio; CHAIM, Tiffany; SERPA, Mauricio; BUSATTO, Geraldo; GATTAZ, Wagner; VALENTE, Kette D.Purpose: Some variants of the brain derived neurotrophic factors (BDNF) gene, namely the Val66Met (rs6265), may contribute the risk for epilepsy development. We aimed to investigate if this polymorphism was associated with the risk for epilepsy development in TLE-HS and its correlation with epilepsy-related factors and the presence of psychiatric disorders. Methods: We assessed 119 patients with unequivocal TLE-HS and 112 healthy controls. Individuals were genotyped for the polymorphisms of the gene encoding BDNF Val66Met. Results: There was no difference between TLE-HS and healthy controls, for the genotypic distribution (p = 0.636) and allelic distribution (p = 0.471). There was no correlation between Val66Met and epilepsy-related factors and for psychiatric comorbidities (p = 0.888). Conclusions: Our findings demonstrated that polymorphism Val66Met is not associated with TLE-HS, epilepsy-related factors and psychiatric comorbidities in this selected group of patients.
- Donepezil effects on cholesterol and oxysterol plasma levels of Alzheimer's disease patients(2018) COSTA, Alana C.; JOAQUIM, Helena P. G.; NUNES, Valeria S.; KERR, Daniel S.; FERREIRA, Guilherme S.; FORLENZA, Orestes V.; GATTAZ, Wagner F.; TALIB, Leda LemeCholesterol is an essential component in the structure and function of cell membranes and has been associated with the major pathological signatures of Alzheimer's disease (AD). To maintain brain cholesterol homeostasis, it is converted into 24(S)-hydroxycholesterol (24OHC) which can be driven through the blood-brain barrier. Several studies have already described a decrease in 24OHC and an increase of 27(S)-hydroxycholesterol (27OHC) in AD, as a reflection of disease burden, the loss of metabolically active neurons and the degree of structural atrophy. It is also well known that peripheral cholesterol is altered in AD patients. However, there are no data regarding effects of AD treatment in this cholesterol pathway. Since a study from our group indicated a significant increase in membrane phospholipid metabolism by donepezil, the aim of this study was to evaluate the effect of short- and long-term donepezil treatment on cholesterol and metabolites 24OHC and 27OHC in plasma of AD patients and in healthy volunteers. At baseline, we found a decrease of 24OHC (p = 0.003) in AD patients. Cholesterol levels increased with donepezil treatment (p = 0.04) but no differences were observed regarding 24OHC and 27OHC. However, these results confirm and extend previous studies demonstrating disturbed cholesterol turnover in Alzheimer's disease.