Baligand Celine, Barret Olivier, Tourais Amélie, Pérot Jean-Baptiste, Thenadey Didier, Petit Fanny, Liot Géraldine, Gaillard Marie-Claude, Flament Julien, Dhenain Marc, Valette Julien
Laboratoire des Maladies Neurodégénératives, MIRCen, CNRS, CEA, Université Paris-Saclay, F-92260 Fontenay-aux-Roses, France.
Metabolites. 2021 Apr 22;11(5):263. doi: 10.3390/metabo11050263.
The cerebral metabolic rate of oxygen consumption (CMRO) is a key metric to investigate the mechanisms involved in neurodegeneration in animal models and evaluate potential new therapies. CMRO can be measured by direct O magnetic resonance imaging (O-MRI) of HO signal changes during inhalation of O-labeled oxygen gas. In this study, we built a simple gas distribution system and used 3D zero echo time (ZTE-)MRI at 11.7 T to measure CMRO in the APP/PS1 mouse model of amyloidosis. We found that CMRO was significantly lower in the APP/PS1 brain than in wild-type at 12-14 months. We also estimated cerebral blood flow (CBF) from the post-inhalation washout curve and found no difference between groups. These results suggest that the lower CMRO observed in APP/PS1 is likely due to metabolism impairment rather than to reduced blood flow. Analysis of the O-MRI data using different quantification models (linear and 3-phase model) showed that the choice of the model does not affect group comparison results. However, the simplified linear model significantly underestimated the absolute CMRO values compared to a 3-phase model. This may become of importance when combining several metabolic fluxes measurements to study neuro-metabolic coupling.
脑氧代谢率（CMRO）是研究动物模型神经退行性变机制和评估潜在新疗法的关键指标。CMRO可通过在吸入O标记氧气期间对HO信号变化进行直接氧磁共振成像（O-MRI）来测量。在本研究中，我们构建了一个简单的气体分配系统，并使用11.7 T的3D零回波时间（ZTE-）MRI来测量淀粉样变性APP/PS1小鼠模型中的CMRO。我们发现，在12至14个月时，APP/PS1小鼠脑内的CMRO显著低于野生型小鼠。我们还从吸入后洗脱曲线估计了脑血流量（CBF），发现两组之间没有差异。这些结果表明，在APP/PS1小鼠中观察到的较低CMRO可能是由于代谢受损而非血流量减少所致。使用不同量化模型（线性和三相模型）对O-MRI数据进行分析表明，模型的选择不影响组间比较结果。然而，与三相模型相比，简化的线性模型显著低估了绝对CMRO值。当结合多个代谢通量测量来研究神经代谢耦合时，这可能具有重要意义。
