Acute administration of ketone beta-hydroxybutyrate downregulates 7T proton magnetic resonance spectroscopy-derived levels of anterior and posterior cingulate GABA and glutamate in healthy adults
Acute administration of ketone beta-hydroxybutyrate downregulates 7T proton magnetic resonance spectroscopy-derived levels of anterior and posterior cingulate GABA and glutamate in healthy adults
复制标题
酮 β-羟基丁酸酯的急性给药下调健康成人中 7T 质子磁共振波谱衍生的前扣带回和后扣带回 GABA 和谷氨酸水平
DOI：
10.1038/s41386-022-01364-8
复制
发表时间：
2022
影响因子：
7.6
通讯作者：
Mujica-Parodi, Lilianne R.
中科院分区：
文献类型：
--
作者：
Hone-Blanchet, Antoine;Antal, Botond;McMahon, Liam;Lithen, Andrew;Smith, Nathan A.;Stufflebeam, Steven;Yen, Yi-Fen;Lin, Alexander;Jenkins, Bruce G.;Mujica-Parodi, Lilianne R.
葡萄糖代谢在大脑老化和几种神经系统疾病中受损。在保护衰老大脑的背景下，已经报道了酮的有益作用，然而，它们的神经生理学作用在很大程度上仍然没有表征，阻碍了它们作为有效治疗选择的发展。在这份报告中，我们研究了急性给药酮d-β-羟基丁酸酯（d-β HB）单酯在空腹健康受试者中的神经化学作用，采用超高场质子磁共振波谱（MRS）。在两项受试者内代谢干预实验中，在空腹健康受试者中获得了7 T MRS数据（1）d-β HB给药前和给药后的前扣带回皮质（N = 16），以及（2）d-β HB给药前和给药后的后扣带回皮质（N = 26），与活性对照葡萄糖相比。通过年龄、d-β HB和葡萄糖水平的影响，进一步探讨d-β HB和葡萄糖对MRS代谢产物的影响。结果表明，d-β HB可显著降低大鼠大脑前、后皮质GABA和Glu的含量。重要的是，该效应是特异性的tod-β HB，在给予葡萄糖后未观察到。对GABA和Glu的影响程度与年龄和d-β HB血液水平的升高显著相关。总之，我们的研究结果表明，与正常的能量底物葡萄糖相比，酮的给药严重影响了整个禁食皮层中的主要抑制性和兴奋性递质。重要的是，这种影响在老年时会增加，这表明随着大脑老化对酮的敏感性增加。
Glucose metabolism is impaired in brain aging and several neurological conditions. Beneficial effects of ketones have been reported in the context of protecting the aging brain, however, their neurophysiological effect is still largely uncharacterized, hurdling their development as a valid therapeutic option. In this report, we investigate the neurochemical effect of the acute administration of a ketone d-beta-hydroxybutyrate (d-βHB) monoester in fasting healthy participants with ultrahigh-field proton magnetic resonance spectroscopy (MRS). In two within-subject metabolic intervention experiments, 7 T MRS data were obtained in fasting healthy participants (1) in the anterior cingulate cortex pre- and post-administration ofd-βHB (N= 16), and (2) in the posterior cingulate cortex pre- and post-administration ofd-βHB compared to active control glucose (N= 26). Effect of age and blood levels ofd-βHB and glucose were used to further explore the effect ofd-βHB and glucose on MRS metabolites. Results show that levels of GABA and Glu were significantly reduced in the anterior and posterior cortices after administration ofd-βHB. Importantly, the effect was specific tod-βHB and not observed after administration of glucose. The magnitude of the effect on GABA and Glu was significantly predicted by older age and by elevation of blood levels ofd-βHB. Together, our results show that administration of ketones acutely impacts main inhibitory and excitatory transmitters in the whole fasting cortex, compared to normal energy substrate glucose. Critically, such effects have an increased magnitude in older age, suggesting an increased sensitivity to ketones with brain aging.
登录
查看更多内容
影响因子：
15.9
作者：
Mergenthaler P;Lindauer U;Dienel GA;Meisel A
通讯作者：
Meisel A
生酮饮食治疗癫痫
影响因子：
13.8
作者：
Marjorie Dixon
通讯作者：
Marjorie Dixon
大脑区域葡萄糖代谢，神经精神症状和出现的风险轻度认知障碍：梅奥诊所的衰老研究。
DOI：
10.1016/j.jagp.2020.06.006
发表时间：
2021-03
期刊：
The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry
影响因子：
--
作者：
Krell-Roesch J;Syrjanen JA;Vassilaki M;Lowe VJ;Vemuri P;Mielke MM;Machulda MM;Stokin GB;Christianson TJ;Kremers WK;Jack CR Jr;Knopman DS;Petersen RC;Geda YE
通讯作者：
Geda YE
生酮饮食与常规护理治疗顽固性癫痫儿童和青少年的长期临床结果和经济评估
影响因子：
2.2
作者：
B. Wijnen;R. Kinderen;D. Lambrechts;D. Postulart;A. Aldenkamp;M. Majoie;S. Evers
通讯作者：
S. Evers
当β-羟基丁酸取代培养神经元中的葡萄糖时，神经递质谷氨酸的可用性会降低
影响因子：
4.7
作者：
T. M. Lund;Ø. Risa;U. Sonnewald;A. Schousboe;H. Waagepetersen
通讯作者：
H. Waagepetersen