RESUMO
Taurine (2-aminoethanesulfonic acid) is a non-protein ß-amino acid essential for cellular homeostasis, with antioxidant, anti-inflammatory, and cytoprotective properties that are crucial for life maintenance. This study aimed to evaluate the effects of taurine administration on hippocampal neurogenesis, neuronal preservation, or reverse damage in rats exposed to forced ethanol consumption in an animal model. Wistar rats were treated with ethanol (EtOH) for a 28-day period (5% in the 1st week, 10% in the 2nd week, and 20% in the 3rd and 4th weeks). Two taurine treatment protocols (300 mg/kg i.p.) were implemented: one during ethanol consumption to analyze neuroprotection, and another after ethanol consumption to assess the reversal of ethanol-induced damage. Overall, the results demonstrated that taurine treatment was effective in protecting against deficits induced by ethanol consumption in the dentate gyrus. The EtOH+TAU group showed a significant increase in cell proliferation (145.8%) and cell survival (54.0%) compared to the EtOH+Sal group. The results also indicated similar effects regarding the reversal of ethanol-induced damage 28 days after the cessation of ethanol consumption. The EtOH+TAU group exhibited a significant increase (41.3%) in the number of DCX-immunoreactive cells compared to the EtOH+Sal group. However, this amino acid did not induce neurogenesis in the tissues of healthy rats, implying that its activity may be contingent upon post-injury stimuli.
Assuntos
Proteína Duplacortina , Etanol , Hipocampo , Neurogênese , Fármacos Neuroprotetores , Ratos Wistar , Taurina , Animais , Taurina/farmacologia , Neurogênese/efeitos dos fármacos , Masculino , Fármacos Neuroprotetores/farmacologia , Ratos , Hipocampo/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Giro Denteado/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de DoençasRESUMO
Therapeutic hypothermia (TH) is well established as a standard treatment for term and near-term infants. However, therapeutic effects of hypothermia following neonatal anoxia in very premature babies remains inconclusive. The present rodent model of preterm neonatal anoxia has been shown to alter developmental milestones and hippocampal neurogenesis, and to disrupt spatial learning and memory in adulthood. These effects seem to be reduced by post-insult hypothermia. Epigenetic-related mechanisms have been postulated as valuable tools for developing new therapies. Dentate gyrus neurogenesis is regulated by epigenetic factors. This study evaluated whether TH effects in a rodent model of preterm oxygen deprivation are based on epigenetic alterations. The effects of TH on both developmental features (somatic growth, maturation of physical characteristics and early neurological reflexes) and performance of behavioral tasks at adulthood (spatial reference and working memory, and fear conditioning) were investigated in association with the possible involvement of the epigenetic operator Enhancer of zeste homolog 2 (Ezh2), possibly related to long-lasting effects on hippocampal neurogenesis. Results showed that TH reduced both anoxia-induced hippocampal neurodegeneration and anoxia-induced impairments on risk assessment behavior, acquisition of spatial memory, and extinction of auditory and contextual fear conditioning. In contrast, TH did not prevent developmental alterations caused by neonatal anoxia and did not restore hippocampal neurogenesis or cause changes in EZH2 levels. In conclusion, despite the beneficial effects of TH in hippocampal neurodegeneration and in reversing disruption of performance of behavioral tasks following oxygen deprivation in prematurity, these effects seem not related to developmental alterations and hippocampal neurogenesis and, apparently, is not caused by Ezh2-mediated epigenetic alteration.
Assuntos
Hipocampo/crescimento & desenvolvimento , Hipotermia Induzida/métodos , Hipóxia Encefálica/fisiopatologia , Hipóxia Encefálica/terapia , Memória Espacial/fisiologia , Animais , Animais Recém-Nascidos , Feminino , Hipóxia Encefálica/psicologia , Lactação/fisiologia , Masculino , Ratos , Ratos Wistar , Resultado do TratamentoRESUMO
Ethanol intake may cause alterations in cellular metabolism altering motricity, learning and cognition. The cerebellum is one of the most susceptible organs to ethanol-related disorders during development, and is associated with oxidative stress-induced apoptosis being crucial for pathogenic consequences. The UChA variety is a special strain of Wistar rat genetically selected and represents a rare model for the studies related to genetic, biochemical, physiological, nutritional, and pharmacological effects of ethanol. We evaluated the structure and apoptosis in the cerebellar white matter of UChA rats. There were two groups of 09 rats: a control group that did not consume ethanol, and an experimental group of UChA rats that consumed ethanol at 10% (v/v) (<2 g ethanol/kg body weight/day). At 120 days old, rats were anaesthetized followed by decapitation, and their cerebella were collected and fixed. Cerebellar sections were subjected to immunohistochemistry for Caspase-3 and XIAP and transmission electron microscopy (TEM). The UChA group showed more glial cells immunoreactive for caspase-3 and less for XIAP than control group. Alcohol consumption affected myelin integrity. Severe ultrastructural damages in UChA group were observed such as disruption of the myelin sheath, disorganization and deformation of its components, and an increase in the interaxonal spaces. In conclusion, our data demonstrated that ethanol induced apoptosis in the glial cells and promoted an intense change in the myelin sheath of UChA rats, which may cause functional disorders.
Assuntos
Apoptose/efeitos dos fármacos , Axônios/efeitos dos fármacos , Neuroglia/efeitos dos fármacos , Substância Branca/efeitos dos fármacos , Consumo de Bebidas Alcoólicas , Animais , Axônios/patologia , Axônios/ultraestrutura , Caspase 3/biossíntese , Etanol/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas Inibidoras de Apoptose/biossíntese , Microscopia Eletrônica de Transmissão , Neuroglia/patologia , Neuroglia/ultraestrutura , Ratos , Ratos Wistar , Substância Branca/patologia , Substância Branca/ultraestruturaRESUMO
Ethanol alters motricity, learning, cognition, and cellular metabolism in the cerebellum. We evaluated the effect of ethanol on apoptosis in Golgi, Purkinje, and granule cells of the cerebellum in adult rats. There were two groups of 20 rats: a control group that did not consume ethanol and an experimental group of UChA rats that consumed ethanol at 10% (<2 g ethanol/kg body weight/day). At 120 days old, rats were anesthetized and decapitated, and their cerebella were collected and fixed. Cerebellar sections were subjected to immunohistochemistry for terminal deoxynucleotide transferase dUTP nick end labeling (TUNEL), caspase-3, X-linked inhibitor of apoptosis protein (XIAP), and insulin-like growth factor 1-receptor (IGF-1R); real-time PCR (RT-PCR) to determine caspase-3, XIAP, and IGF-1R gene expression; and transmission electron microscopy (TEM). We identified fragmentation of DNA and an increase in caspase-3 protein and XIAP in Purkinje cells, whereas granule cells exhibited increased caspase-3 and XIAP. IGF-1R expression was unchanged. There was no significant difference in gene expression of caspase-3, XIAP, and IGF-1R. There were an increase in lipid droplets, a reduction in the cellular cytoplasm in electron-dense nuclei, and changes in the myelin sheath in the cerebellar cortex. In conclusion, our data demonstrated that ethanol induced apoptosis in the Purkinje and granule cells of the cerebellum of adult UChA rats.
Assuntos
Apoptose/efeitos dos fármacos , Depressores do Sistema Nervoso Central/administração & dosagem , Cerebelo/efeitos dos fármacos , Etanol/administração & dosagem , Neurônios/efeitos dos fármacos , Animais , Apoptose/fisiologia , Caspase 3/metabolismo , Cerebelo/patologia , Cerebelo/fisiopatologia , Citoplasma/efeitos dos fármacos , Citoplasma/metabolismo , Citoplasma/patologia , Fragmentação do DNA/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Proteínas Inibidoras de Apoptose/metabolismo , Gotículas Lipídicas/efeitos dos fármacos , Gotículas Lipídicas/metabolismo , Gotículas Lipídicas/patologia , Masculino , Microscopia Eletrônica de Transmissão , Bainha de Mielina/efeitos dos fármacos , Bainha de Mielina/patologia , Bainha de Mielina/fisiologia , Neurônios/patologia , Neurônios/fisiologia , Ratos , Reação em Cadeia da Polimerase em Tempo Real , Receptor IGF Tipo 1/metabolismoRESUMO
The appearance, the odor, and the flavor of foods, all send messages to the encephalic area of the brain. The hypothalamus, in particular, plays a key role in the mechanisms that control the feeding behavior. These signals modulate the expression and the action of anorexigenic or orexigenic substances that influence feeding behavior. The serotonergic system of neurotransmission consists of neurons that produce and liberate serotonin as well as the serotonin-specific receptor. It has been proven that some serotonergic drugs are effective in modulating the mechanisms of control of feeding behavior. Obesity and its associated illnesses have become significant public health problems. Some drugs that manipulate the serotonergic systems have been demonstrated to be effective interventions in the treatment of obesity. The complex interplay between serotonin and its receptors, and the resultant effects on feeding behavior have become of great interest in the scientific community.
Assuntos
Comportamento Alimentar/fisiologia , Serotonina/fisiologia , Animais , Colecistocinina/fisiologia , Metabolismo Energético/fisiologia , Comportamento Alimentar/efeitos dos fármacos , Homeostase , Humanos , Hipotálamo/fisiologia , Neurônios/fisiologia , Neuropeptídeo Y/fisiologia , Pró-Opiomelanocortina/fisiologia , Receptores de Serotonina/fisiologia , Transmissão SinápticaRESUMO
To analyze the differential recruitment of the raphe nuclei during different phases of feeding behavior, rats were subjected to a food restriction schedule (food for 2 h/day, during 15 days). The animals were submitted to different feeding conditions, constituting the experimental groups: search for food (MFS), food ingestion (MFI), satiety (MFSa) and food restriction control (MFC). A baseline condition (BC) group was included as further control. The MFI and MFC groups, which presented greater autonomic and somatic activation, had more FOS-immunoreactive (FOS-IR) neurons. The MFI group presented more labeled cells in the linear (LRN) and dorsal (DRN) nuclei; the MFC group showed more labeling in the median (MRN), pontine (PRN), magnus (NRM) and obscurus (NRO) nuclei; and the MFSa group had more labeled cells in the pallidus (NRP). The BC exhibited the lowest number of reactive cells. The PRN presented the highest percentage of activation in the raphe while the DRN the lowest. Additional experiments revealed few double-labeled (FOS-IR+5-HT-IR) cells within the raphe nuclei in the MFI group, suggesting little serotonergic activation in the raphe during food ingestion. These findings suggest a differential recruitment of raphe nuclei during various phases of feeding behavior. Such findings may reflect changes in behavioral state (e.g., food-induced arousal versus sleep) that lead to greater motor activation, and consequently increased FOS expression. While these data are consistent with the idea that the raphe system acts as gain setter for autonomic and somatic activities, the functional complexity of the raphe is not completely understood.