RESUMEN
Chronic alcoholism seriously damages the central nervous system and leads to impaired learning and memory. Cell damage in chronic alcoholism is strongly associated with elevated levels of hydrogen sulfide (H2S) and calcium ion overload. Aminooxyacetic acid is a cystathionine-ß-synthase activity inhibitor that can reduce H2S formation in the brain. This study sought to observe the effect of aminooxyacetic acid on learning and memory in a chronic alcoholism rat model. Rats were randomly divided into three groups. Rats in the control group were given pure water for 28 days. Rats in the model group were given 6% alcohol for 28 days to establish an alcoholism rat model. Rats in the aminooxyacetic acid remedy group were also given 6% alcohol for 28 days and were also intraperitoneally injected daily with aminooxyacetic acid (5 mg/kg) from day 15 to day 28. Learning and memory was tested using the Morris water maze test. The ultrastructure of mitochondria in the hippocampus was observed by electron microscopy. H2S levels in the hippocampus were measured indirectly by spectrophotometry, and ATPase activity was measured using a commercial kit. The expression of myelin basic protein was determined by immunohistochemistry and western blotting. Compared with the control group, latency and swimming distance were prolonged in the navigation test on days 2, 3, and 4 in the model group. In the spatial probe test on day 5, the number of platform crosses was reduced in the model group. Cristae cracks, swelling or deformation of mitochondria appeared in the hippocampus, the hippocampal H2S level was increased, the mitochondrial ATPase activity was decreased, and the expression of myelin basic protein in the hippocampus was down-regulated in the model group compared with the control group. All the above indexes were ameliorated in the aminooxyacetic acid remedy group compared with the model group. These findings indicate that aminooxyacetic acid can improve learning and memory in a chronic alcoholism rat model, which may be associated with reduction of hippocampal H2S level and mitochondrial ATPase activity, and up-regulation of myelin basic protein levels in the hippocampus.
RESUMEN
OBJECTIVE: To investigate the effects of aminooxyacetic acid (AOAA) on learning and memory ability and possible mechanisms in rats with chronic alcoholism. METHODS: Sixty SD male rats were randomly divided into three groups on average.The model group rats and the remedy group rats were fed with the water containing (v/v) 6% alcohol for 28 days.After 14 days, the remedy group rats were treated with AOAA (5 mg/kg·d) by intraperitoneal injection once a day for 14 days and the other two group rats were treated with the equal amount of saline by intraperitoneal injection every day.Five days before the end of the experiment, the water maze test was carried out to test the learning and memory ability of rats for 5 days.Subsequently, the content of H2S, the activity of ATP enzyme and the expression of 5-HT in hippocampus were measured. RESULTS: Compared with the rats in the control group, the latency and the swimming distance of the 2nd to the 4th day, the content of H2S in hippocampus of rats in the model group were all increased, the mitochondrial ATP enzyme activity in hippocampus and the positive expression of 5-HT in hippocampus CA1 and CA3 of rats in the model group were decreased (P<0.01).Compared with the rats in the model group, the latency and the swimming distance of the 2nd to the 4th day, the content of H2S in hippocampus of the rats in the remedy group were decreased, the mitochondrial ATP enzyme activity in hippocampus and the positive expression of 5-HT in hippocampus CA1 and CA3 of rats in the model group were increased (P<0.01). CONCLUSIONS: AOAA could alleviate the symptoms of chronic alcoholism rats, which may be related to the effects of AOAA on the content of H2S, the mitochondrial enzyme activity and the expression of 5-HT in hippocampus.