Choi In-Young, Wang Wen-Tung, Smirnova Irina V, Lee Phil
Department of Neurology, University of Kansas Medical Center, 4000 Cambridge Street, Mail Stop 4032, Kansas City, KS, 66160, USA.
Department of Radiology, University of Kansas Medical Center, Kansas City, KS, 66160, USA.
Neurochem Res. 2025 Mar 31;50(2):132. doi: 10.1007/s11064-025-04385-z.
Cerebral ketone bodies are crucial for understanding both physiological brain metabolism and pathological states, such as diabetic ketoacidosis (DKA). However, the metabolic consequences of elevated ketone body levels on brain metabolism during DKA remain poorly described to date. In this study, we utilized non-invasive magnetic resonance spectroscopy to detect and quantify ketone bodies and their correlation with neurotransmitter and neurotransmitter precursor levels in situ in the living brain of the streptozotocin (STZ)-induced type 1 diabetes (T1D) rat model. This well-characterized T1D model develops insulin deficiency with chronic hyperglycemia, which can trigger DKA. We report the detection and quantification of the acetone signal at 2.22 ppm in the STZ-induced T1D rat brain, along with two other ketone bodies, β-hydroxybutyrate and acetoacetate at 9.4 T. Cerebral levels of all three ketone bodies significantly increased as diabetes progressed compared to baseline levels prior to STZ injection. Moreover, ketone body levels correlated strongly with the inhibitory neurotransmitter γ-aminobutyric acid (GABA) and glutamine, as well as several other neurochemicals. Overall, DKA is characterized by a marked increase in brain ketone bodies as T1D progresses, accompanied by elevated GABA and glutamine levels. This study demonstrates the direct measurement of ketone bodies in the brain in vivo, enabling further investigation of their impact on brain metabolism in both health and disease.
脑酮体对于理解生理性脑代谢和诸如糖尿病酮症酸中毒（DKA）等病理状态至关重要。然而，迄今为止，关于DKA期间酮体水平升高对脑代谢的代谢后果仍描述甚少。在本研究中，我们利用非侵入性磁共振波谱技术在链脲佐菌素（STZ）诱导的1型糖尿病（T1D）大鼠模型的活体脑中原位检测和定量酮体及其与神经递质和神经递质前体水平的相关性。这个特征明确的T1D模型会出现胰岛素缺乏伴慢性高血糖，进而可引发DKA。我们报告了在9.4 T磁场下，在STZ诱导的T1D大鼠脑中检测和定量2.22 ppm处的丙酮信号，以及另外两种酮体β-羟基丁酸酯和乙酰乙酸酯。与STZ注射前的基线水平相比，随着糖尿病进展，所有三种酮体的脑内水平均显著升高。此外，酮体水平与抑制性神经递质γ-氨基丁酸（GABA）和谷氨酰胺以及其他几种神经化学物质密切相关。总体而言，随着T1D进展，DKA的特征是脑酮体显著增加，同时伴有GABA和谷氨酰胺水平升高。本研究证明了在体内直接测量脑内酮体，从而能够进一步研究其在健康和疾病状态下对脑代谢的影响。
