Carrillo-de Sauvage Maria-Angeles, Flament Julien, Bramoulle Yann, Ben Haim Lucile, Guillermier Martine, Berniard Aurélie, Aurégan Gwennaëlle, Houitte Diane, Brouillet Emmanuel, Bonvento Gilles, Hantraye Philippe, Valette Julien, Escartin Carole
1] Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Département des Sciences du Vivant (DSV), Institut d'Imagerie Biomédicale (I2BM), MIRCen, Fontenay-aux-Roses, France [2] Neurodegenerative Diseases Laboratory, Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud, UMR 9199, Fontenay-aux-Roses, France.
1] Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Département des Sciences du Vivant (DSV), Institut d'Imagerie Biomédicale (I2BM), MIRCen, Fontenay-aux-Roses, France [2] Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Service UMS 27, Fontenay-aux-Roses, France.
J Cereb Blood Flow Metab. 2015 Jun;35(6):917-21. doi: 10.1038/jcbfm.2015.48. Epub 2015 Apr 1.
Ciliary neurotrophic factor (CNTF) is neuroprotective against multiple pathologic conditions including metabolic impairment, but the mechanisms are still unclear. To delineate CNTF effects on brain energy homeostasis, we performed a multimodal imaging study, combining in vivo proton magnetic resonance spectroscopy, high-performance liquid chromatography analysis, and in situ glutamate imaging by chemical exchange saturation transfer. Unexpectedly, we found that CNTF expression through lentiviral gene transfer in the rat striatum significantly decreased the levels of neuronal metabolites (N-acetyl-aspartate, N-acetyl-aspartyl-glutamate, and glutamate). This preclinical study shows that CNTF remodels brain metabolism, and suggests that decreased levels of neuronal metabolites may occur in the absence of neuronal dysfunction.
睫状神经营养因子（CNTF）对包括代谢损伤在内的多种病理状况具有神经保护作用，但其机制仍不清楚。为了阐明CNTF对脑能量稳态的影响，我们进行了一项多模态成像研究，结合体内质子磁共振波谱、高效液相色谱分析和通过化学交换饱和转移进行的原位谷氨酸成像。出乎意料的是，我们发现通过慢病毒基因转移在大鼠纹状体中表达CNTF会显著降低神经元代谢物（N-乙酰天门冬氨酸、N-乙酰天门冬氨酰谷氨酸和谷氨酸）的水平。这项临床前研究表明，CNTF重塑脑代谢，并提示在无神经元功能障碍的情况下可能会出现神经元代谢物水平降低。
