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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Medial-frontal cortex hypometabolism in chronic phencyclidine exposed rats assessed by high resolution magic angle spin 11.7 T proton magnetic resonance spectroscopy
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Medial-frontal cortex hypometabolism in chronic phencyclidine exposed rats assessed by high resolution magic angle spin 11.7 T proton magnetic resonance spectroscopy

机译：高分辨率魔角旋转11.7 T质子磁共振波谱评估慢性苯环利定暴露大鼠的内侧额叶皮层低代谢

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Background: Proton magnetic resonance spectroscopy ( 1H-MRS) clinical studies of patients with schizophrenia document prefrontal N-acetylaspartate (NAA) reductions, suggesting an effect of the disease or of antipsychotic medications. We studied in the rat the effect of prolonged exposure to a low-dose of the NMDA glutamate receptor antagonist phencyclidine (PCP) on levels of NAA, glutamate and glutamine in several brain regions where metabolite reductions have been reported in chronically medicated patients with schizophrenia. Methods: Two groups of ten rats each were treated with PCP (2.58 mg/kg/day) or vehicle and were sacrificed after 1 month treatment. Concentrations of neurochemicals were determined with high resolution magic angle (HR-MAS) 1H-MRS at 11.7 T in ex vivo punch biopsies from the medial frontal and cingulate cortex, striatum, nucleus accumbens, amygdala and ventral hippocampus. Results: PCP treatment reduced NAA, glutamate, glycine, aspartate, creatine, lactate and GABA in medial frontal cortex. In the nucleus accumbens, PCP reduced levels of NAA, aspartate and glycine; similarly aspartate and glycine were reduced in the striatum. Finally the amygdala and hippocampus had elevations in glutamine and choline, respectively. Conclusions: Low-dose PCP in rats models prefrontal NAA and glutamate reductions documented in chronically-ill schizophrenia patients. Chronic glutamate NMDA receptor blockade in rats replicates an endophenotype in schizophrenia and may contribute to the prefrontal hypometabolic state in schizophrenia.
机译：背景：精神分裂症患者的质子磁共振波谱（1H-MRS）临床研究证明前额叶N-乙酰天冬氨酸（NAA）降低，表明该疾病或抗精神病药物的疗效。我们在大鼠中研究了长期暴露于低剂量的NMDA谷氨酸受体拮抗剂苯环利定（PCP）对几种大脑区域中NAA，谷氨酸和谷氨酰胺水平的影响，据报道，慢性药物治疗的精神分裂症患者体内代谢产物减少。方法：两组，每组十只大鼠分别接受PCP（2.58 mg / kg / day）或溶媒治疗，治疗1个月后处死。在离体前额和扣带状皮层，纹状体，伏隔核，杏仁核和腹侧海马的活体活检中，以高分辨率的魔角（HR-MAS）1H-MRS在11.7 T下测定神经化学物质的浓度。结果：五氯苯酚处理可降低额叶内侧额叶皮质的NAA，谷氨酸，甘氨酸，天冬氨酸，肌酸，乳酸和GABA。在伏隔核中，五氯苯酚会降低NAA，天冬氨酸和甘氨酸的水平;同样，纹状体中的天冬氨酸和甘氨酸减少。最后，杏仁核和海马体的谷氨酰胺和胆碱分别升高。结论：低剂量PCP在大鼠中模拟了慢性病精神分裂症患者的前额叶NAA和谷氨酸的减少。大鼠慢性谷氨酸NMDA受体阻断在精神分裂症中复制内表型，并且可能导致精神分裂症的前额叶代谢不足状态。

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