In vivo Detection and Correlation of Cerebral Ketone Bodies with Neurotransmitters in Streptozotocin-Induced Type 1 Diabetic Rats

Abstract

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.