RESUMO
The main characteristic of brain aging is an exacerbated inflammatory and oxidative response that affects dendritic morphology and the function of the neurons of the prefrontal cortex (PFC) and the hippocampus. This consequently causes memory loss. Recently, the use of the Goji berry (Lycium barbarum) as an antioxidant extract has provided neuroprotection and neuroplasticity, however, its therapeutic potential has not been demonstrated in aging conditions. The objective of this study was to evaluate the effect of Goji administration on memory recognition, as well as the changes in the dendritic morphology of the PFC and Hippocampus pyramidal neurons in old rats. Goji (3 g/kg) was administrated for 60 days in 18-month-old rats. After the treatment, recognition memory was evaluated using the new object recognition task (NORt). The changes in the neuron morphology of the PFC and hippocampus pyramidal neurons in old rats were evaluated by Golgi-cox stain and immunoreactivity for synaptophysin, glial fibrillary acidic protein (GFAP), caspase-3, 3-nitrotyrosine (3-NT) and nuclear factor erythroid 2-related factor 2 (Nrf2). The rats treated with Goji showed a significant increase in dendritic morphology in the PFC and hippocampus neurons, a greater immunoreactivity to synaptophysin and a decrease in reactive astrogliosis and also in caspase-3, in 3-NT and in Nrf2 in these brain regions was also observed. Goji administration promotes the plasticity processes in the PFC and in the hippocampus of old rats, critical structures in the brain aging process.
Assuntos
Envelhecimento/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Lycium/química , Plasticidade Neuronal/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Córtex Pré-Frontal/efeitos dos fármacos , Envelhecimento/genética , Envelhecimento/metabolismo , Animais , Antioxidantes/administração & dosagem , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Caspase 3/genética , Caspase 3/metabolismo , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Humanos , Masculino , Fator de Transcrição NF-E2/genética , Fator de Transcrição NF-E2/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/fisiopatologia , Ratos , Ratos Sprague-DawleyRESUMO
Paclitaxel (Px) is a cancer chemotherapeutic agent that causes bone marrow (BM) cytotoxicity by microtubule stabilization and by modifications in the expression of several genes. Hematopoietic progenitors show severe alterations following Px injury. Erythropoietic recovery should be accompanied by changes in the expression of transcription factors such as c-MYB, GATA-1, NF-E2, Bcl-x(L), and erythropoietin receptor (Epo-R). The aim of this work was to study the in vivo recovery of erythropoiesis and to correlate transcription factors, Bcl-x(L), and Epo-R expressions to apoptosis and changes in proliferation of murine erythroid progenitors following a single dose of Px (29 mg/kg, i.p.). BM total and differential cellularities, apoptosis (TdT-mediated dUTP Nick-End Labeling [TUNEL] assay), clonogenic assays, and immunoblots for transcription factors, Epo-R, and Bcl-x(L) were performed each day for 5 days post-injury. Apoptosis (24 +/- 0.81%, P < 0.01), inhibition of colony growth (burst-forming units-erythroid [BFU-E] and granulocyte-erythroid-macrophage [GEM]), and decrease in BM cellularities (28 +/- 4.2% of control) were maximal at 24 h following Px. The highest apoptosis was concomitant with the lowest BM cellularities. Apoptosis returned to normal values (3.08 +/- 0.61%) by day 3 post-Px. Up-regulation of c-MYB, GATA-1, Epo-R, and Bcl-x(L) expressions were observed between 24 and 48 h following Px. Correlations among c-MYB, GATA-1, Bcl-x(L), and Epo-R were extremely significant. Maximal expression of NF-E2 was observed on day 3 concomitant with the rise (threefold) of early erythroid precursors (BFU-E). Thus, cells that survive injury seem to be stimulated to produce early (24-48 h) erythroid-related and antiapoptotic proteins. Therefore, the results suggest an in vivo interplay between specific transcription factors and Bcl-x(L) during progenitor cell survival and proliferation; mechanisms triggered to restore size and composition of the erythroid compartment.
Assuntos
Antineoplásicos Fitogênicos/toxicidade , Apoptose/efeitos dos fármacos , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Eritropoese/efeitos dos fármacos , Genes myb/genética , Paclitaxel/toxicidade , Receptores da Eritropoetina/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Animais , Células da Medula Óssea/efeitos dos fármacos , Sobrevivência Celular , Ensaio de Unidades Formadoras de Colônias , Células Precursoras Eritroides/efeitos dos fármacos , Fatores de Ligação de DNA Eritroide Específicos , Feminino , Fator de Transcrição GATA1 , Expressão Gênica/efeitos dos fármacos , Genes bcl-1/genética , Processamento de Imagem Assistida por Computador , Immunoblotting , Marcação In Situ das Extremidades Cortadas , Cinética , Camundongos , Fator de Transcrição NF-E2 , Subunidade p45 do Fator de Transcrição NF-E2 , Receptores da Eritropoetina/biossínteseRESUMO
Steroids hormones modify the hematological features of homozygous sickle cell disease, including the levels of fetal hemoglobin. We used semi-quantitative RT-PCR analysis of GATA-1, GATA-2, NF-E2, and gamma-globin mRNA levels in a two-phase liquid culture system of human adult erythroid cells in order to assay the effect of progesterone upon gene expression. The levels of expression of GATA-1 and gamma-globin mRNA were significantly increased in cells treated with progesterone compared to untreated cells (1.7- to 2.0-fold). Progesterone treatment did not produce any stimulatory effect upon GATA-2 and NF-E2 mRNA expression. Differences in the synthesis of HbF protein could not be detected by flow cytometry, although we observed a small difference in mean intensity fluorescence between cells treated and cells untreated with progesterone on days 7 and 9. Using anti-transferrin receptor and anti-glycophorin A antibodies, we verified that addition of progesterone did not cause any change in erythroid proliferation and differentiation. In conclusion, it is possible that the increased expression of gamma-globin mRNA after progesterone treatment observed in this study may be related to the increased GATA-1 mRNA expression. Interactions of the steroid receptors with the basal transcriptional machinery and with transcription factors might mediate their transcriptional effects.