Dept. Fisiología (Fisiología Animal II), Facultad de Biología, Madrid, Spain.
Neuroscience. 2012 Jan 10;201:12-9. doi: 10.1016/j.neuroscience.2011.11.033. Epub 2011 Nov 22.
Animal models have greatly contributed to the understanding of neuropsychiatric disorders and have provided extensive evidence for the "neurodevelopmental hypothesis." In this regard, a single and prolonged episode (24 h) of early maternal deprivation early in life, on postnatal day 9, has been proposed as an animal model for the investigation of certain neuropsychiatric disorders, including schizophrenia. Since metabolic changes in hippocampus (HIP) and prefrontal cortex (PFC) have been described among schizophrenic patients by using ex vivo high-resolution magic angle spinning (HR-MAS) proton ((1)H) nuclear magnetic resonance spectroscopy, in the present study we aimed to investigate the effects of maternal deprivation (MD) on the metabolite profiles of the developing brain by using the HR-MAS technique. MD significantly altered the hippocampal and cortical metabolic profile of neonatal rats (PND 13) in a sex-dependent manner. Glutamine and glutamate (Glx) and taurine of male and female rat pups were altered in both brain areas analyzed. Differences in hippocampal phosphorylethanolamine have also been found as a function of the MD protocol. In addition, MD induced some other region- and sex-dependent effects, including changes in N-acetyl aspartate and total choline signals in the hippocampi of male pups. Present findings indicate a different brain metabolic profile in our animal model of early life stress suggesting its potential utility in the implementation of translational neuropsychiatric research.
动物模型极大地促进了对神经精神疾病的理解,并为“神经发育假说”提供了广泛的证据。在这方面,生命早期(出生后第 9 天)的单一且持续时间较长(24 小时)的早期母体剥夺已被提议作为研究某些神经精神疾病(包括精神分裂症)的动物模型。由于使用离体高分辨率魔角旋转(HR-MAS)质子(1H)核磁共振波谱术已经在精神分裂症患者中描述了海马(HIP)和前额叶皮层(PFC)中的代谢变化,因此本研究旨在使用 HR-MAS 技术研究母体剥夺(MD)对发育中大脑代谢谱的影响。MD 以性别依赖的方式显着改变了新生大鼠(PND 13)的海马和皮质代谢谱。雄性和雌性幼鼠的谷氨酰胺和谷氨酸(Glx)和牛磺酸在分析的两个脑区均发生改变。还发现了作为 MD 方案函数的海马磷酸乙醇胺的差异。此外,MD 还诱导了其他区域和性别依赖性的影响,包括雄性幼鼠海马中 N-乙酰天冬氨酸和总胆碱信号的变化。目前的研究结果表明,我们的早期生活应激动物模型中存在不同的大脑代谢谱,这表明其在实施转化神经精神研究方面具有潜在的应用价值。