ABSTRACT
Abstract Background Adenosine A1 receptor (AA1R) is widely present in the central nervous system, exerting brain protective antiepileptic effects, mainly by binding corresponding G proteins. We evaluated the neuroprotective effects of AA1R on hippocampal neuronal injury after lithium chloride-pilocarpine-induced epilepsy in rats. Materials and Methods A total of 60 male SD rats were randomly divided into four groups (n = 15/group): normal control, epilepsy, epilepsy + AA1R antagonist (DPCPX), and epilepsy + AA1R agonist (2-CAdo). An epilepsy model was established through kindling by lithium chloride-pilocarpine. The four groups were observed on days 1, 14, and 30. Pathological and morphological changes of hippocampal neurons were observed by HE staining; apoptosis was detected by TUNEL assay. Caspase-3 and GABA receptor expressions were detected by Western blot. Results In the hippocampal CA3 area of the epilepsy group, the cellular structure was not neatly arranged, and some neurons were swelling, thick, and incomplete. Compared with the epilepsy group at the same time point, cells in the epilepsy + DPCPX group had an increased distortion, disorganization, edema, cytoplasmic vacuoles, and degeneration. In the epilepsy + 2-CAdo group, cell arrangement was regular and orderly, and structural damages were lessened. Compared with the normal control group at the same time point, the epilepsy group underwent evident neuronal apoptosis, with a significantly higher apoptotic index (AI) (p < 0.05). Compared with the epilepsy group, the neuronal apoptosis of the epilepsy + DPCPX group was boosted, and the AI significantly increased (p < 0.05). The neuronal apoptosis of the epilepsy + 2-CAdo group was inhibited, and the AI significantly decreased (p < 0.05). Compared with the epilepsy group, the caspase-3 expression levels of the epilepsy + DPCPX group on days 14 and 30 were significantly upregulated (p < 0.05), but those of the epilepsy + 2-CAdo group were significantly downregulated (p < 0.05). Conclusions AA1R abated cell edema and reduced apoptosis, exerting neuroprotective effects on hippocampal neuronal injury after lithium chloride-pilocarpine-induced epilepsy.
Subject(s)
Animals , Male , Rats , Neuroprotective Agents/pharmacology , Epilepsy/drug therapy , Adenosine A1 Receptor Agonists/pharmacology , Hippocampus/drug effects , Pilocarpine/toxicity , Time Factors , Rats, Sprague-Dawley , Apoptosis/drug effects , Lithium Chloride/toxicity , Disease Models, Animal , Hippocampus/pathology , Neurons/pathologyABSTRACT
A aversão alimentar condicionada é uma técnica que pode ser utilizada em animais para evitar a ingestão de plantas tóxicas. O presente estudo teve como objetivo testar a eficiência e durabilidade da aversão alimentar condicionada em caprinos para evitar o consumo de Ipomoea carnea subsp. fistulosa. Foram utilizados 14 caprinos jovens da raça Moxotó, que foram adaptados ao consumo da planta. Inicialmente foi administrada I. carnea subsp. fistulosa dessecada e triturada misturada à ração concentrada por 30 dias e, posteriormente, foi fornecida a planta verde por mais 10 dias. Para constatação da adaptação ao consumo da planta os caprinos foram colocados a pastar em um piquete de 510 m² onde tinha sido plantada I. carnea subsp. fistulosa em uma área de 30m² (10 plantas/m²). No 42º dia de experimento, após a constatação do consumo espontâneo os animais receberam a planta verde individualmente na baia por alguns minutos, e todos os animais que consumiam qualquer quantidade da planta foram tratados com uma solução de LiCl na dose 175mg por kg de peso vivo. Este procedimento repetiu-se por mais dois dias. Posteriormente, os caprinos foram divididos em dois grupos: Grupo 1 com seis animais, quatro deles avertidos e dois não avertidos (facilitadores); e o Grupo 2, com oito caprinos, todos avertidos. Para constatar a eficiência e duração da aversão e a influência de animais facilitadores na durabilidade da aversão, os caprinos foram colocados a pastar, em dias alternados, três dias por semana, durante duas horas, no piquete plantado com I. carnea subsp. fistulosa. Por 12 meses os animais foram monitorados durante o pastejo, identificando-se o consumo e a preferência dos animais pelas plantas presentes no piquete. No Grupo 1 tanto os caprinos avertidos quanto os não avertidos iniciaram a ingerir a planta em 1-6 semanas e gradualmente foram aumentando a planta consumida, mas nunca a ingeriram exclusivamente. Nenhum caprino do Grupo 2 iniciou a ingestão da planta durante os 12 meses de experimento. Após esse período a área do piquete destinada ao plantio de I. carnea subsp. fistulosa foi ampliada para 80m² e os animais foram novamente introduzidos, com tempo de pastejo na área aumentado para quatro horas durante cinco dias na semana. Nesta fase todos os caprinos do Grupo 1 ingeriram a planta em grande quantidade. Os caprinos do Grupo 2 iniciaram gradualmente a ingerir a planta e a aversão se extinguiu, em todos os animais, após dois meses. A concentração de swainsonina em I. carnea subsp. fistulosa foi de 0,052±0,05% (média±SD). Conclui-se que a aversão alimentar condicionada é eficiente para evitar a ingestão de I. carnea subsp. fistulosa. No entanto, a duração da mesma depende, entre outras coisas, da quantidade de planta presente na área de pastoreio e do tempo de exposição e se extingue rapidamente por facilitação social.
Conditioned food aversion is a technique that can be used to train livestock to avoid ingestion of poisonous plants. This study tested the efficacy and durability of conditioned food aversion to eliminate goat's consumption of Ipomoea carnea subsp. fistulosa. We used 14 young Moxotó goats, which were initially adapted to the consumption of the plant by offering dried I. carnea subsp. fistulosa with their concentrate diet for 30 days, and then subsequently providing green plant for another 10 days. To confirm the spontaneous consumption of the plant, the goats were allow to graze in a paddock of 510m² where I. carnea subsp. fistulosa had been planted in an area of 30m² (10 plants/m²). On day 42, 12 goats were offered fresh green plant individually in a pen for a few minutes, and after the consumption of any amount of the plant they were treated orally with a solution of LiCl at a dose 175mg per kg of body weight. This procedure was repeated for two more consecutive days. Thereafter, the goats were divided into two groups: Group 1 with four averted and two non-averted goats; and Group 2 with eight averted goats. To verify the efficacy and duration of aversion, both groups were introduced into the paddock with I. carnea subsp. fistulosa three days a week for two hours daily. In Group 1, with two non-averted and four averted goats, all animals started to ingest the plant after 1-6 weeks of grazing. They continually increased their consumption of the plant, but never consumed the plant exclusively. None of the goats of Group 2 goats started eating the plant during the 12 months of observation. After this period the area of the paddock planted with I. carnea subsp. fistulosa was expanded to 80 m² and grazing time was increased to four hours per day for five days a week. At this stage all the goats in Group 1 ingested the plant in large quantities. The goats from Group 2 gradually started to eat the plant and aversion was extinguished in all animals after two months. Swainsonine concentration of I. carnea subsp. fistulosa was 0.052±0.05% (mean ±SD). It was concluded that conditioned food aversion was effective in reducing goat consumption of I. carnea subsp. fistulosa, but the duration of aversion depends on the time of grazing and amount of plant available. However, the aversion was quickly extinguished by social facilitation when averted animals grazed with non-averted animals.