RESUMO
Telomere 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 1.0âg (Li1) or 2.0âg (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, pâ=â0.0159) and in the parietal cortex (Li1, pâ=â0.0375) 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.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Antipsicóticos/uso terapêutico , Hipocampo/efeitos dos fármacos , Compostos de Lítio/uso terapêutico , Lobo Parietal/efeitos dos fármacos , Homeostase do Telômero/efeitos dos fármacos , Doença de Alzheimer/sangue , Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Animais , Antipsicóticos/sangue , Modelos Animais de Doenças , Hipocampo/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutação/genética , Lobo Parietal/metabolismo , Presenilina-1/genética , Proteínas tau/genéticaRESUMO
OBJECTIVE: Phospholipases A2 (PLA2 ) comprise a family of hydrolytic enzymes that cleave membrane phospholipids and play a key role in cellular homeostasis. Alterations in enzymatic activity have been hypothesized in bipolar disorder (BD). Recent studies suggest that PLA2 activity in platelets may reflect PLA2 activity in the brain. The aim of this study was to determine PLA2 activity in platelets of BD patients. METHODS: We determined the activity of PLA2 subtypes [extracellular, calcium-dependent PLA2 (sPLA2 ), intracellular, calcium-dependent PLA2 (cPLA2 ), and intracellular, calcium-independent PLA2 (iPLA2 )] by a radioenzymatic method in platelets from 20 patients with BD (15 drug-naïve and five drug-free) and from 16 age- and gender-matched healthy controls. RESULTS: We found that iPLA2 , cPLA2 , and sPLA2 activities were lower in drug-naïve patients with BD when compared to the control group (p = 0.017, p < 0.001, and p < 0.001, respectively). CONCLUSIONS: Reduced PLA2 activity at the early stage of BD may disrupt brain function and increase the risk for the disease. Moreover, epidemiological studies show that patients with BD have a fivefold increased risk for developing Alzheimer's disease. Because patients with Alzheimer's disease also have reduced PLA2 activity, the present finding of reduced PLA2 in the BD group may be related to the risk factor for these individuals developing Alzheimer's disease in advanced age.
Assuntos
Transtorno Bipolar , Plaquetas/enzimologia , Encéfalo/enzimologia , Fosfolipases A2/metabolismo , Adulto , Transtorno Bipolar/sangue , Transtorno Bipolar/diagnóstico , Cálcio/metabolismo , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Fosfolipídeos/metabolismo , Escalas de Graduação Psiquiátrica , Fatores de RiscoRESUMO
A role of dopaminergic dysfunction has been postulated in the aetiology of schizophrenia. We hypothesized that variations in the dopamine transporter gene (SLC6A3) may be associated with schizophrenia. We conducted case-control and family based analysis on the polymorphic SLC6A3 variable number tandem repeat (VNTR) in a sample of 220 schizophrenic patients, 226 gender and ethnic matched controls, and 49 additional case-parent trios. No differences were found in allelic or genotypic distributions between cases and controls and no significant transmission distortions from heterozygous parents to schizophrenic offspring were detected. Thus, our results do not support an association of the SLC6A3 VNTR with schizophrenia in our sample.
Assuntos
Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Repetições Minissatélites/genética , Polimorfismo Genético/genética , Esquizofrenia/genética , Alelos , Brasil , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , MasculinoRESUMO
Genes do sistema dopaminérgico são de escolha para a pesquisa de susceptibilidade para a esquizofrenia. Desse modo, possível contribuição do polimorfismo do gene do transportador de dopamina (SLC6A3) no aumento da vulnerabilidade para a esquizofrenia foi investigada no presente estudo. Analisou-se a distribuição do sítio polimórfico do gene do transportador de dopamina (VNTR) em uma população de 220 pacientes com esquizofrenia (critério diagnóstico: DSM-IV) e comparou-se com a distribuição em uma população controle de 226 indivíduos pareados para sexo e etnia. Nenhuma diferença foi observada na distribuição dos alelos entre casos e controles. O mesmo polimorfismo também foi investigado em uma segunda amostra composta por 49 trios (pais e probando). O resultado também foi negativo. Tais dados não dão suporte para a participação do polimorfismo do gene do transportador de dopamina no aumento de susceptibilidade para esquizofrenia na amostra estudada.
