MRI spectroscopic and tractography studies indicate consequences of long-term ketogenic diet

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ORIGINAL ARTICLE

MRI spectroscopic and tractography studies indicate consequences of long‑term ketogenic diet Kinga Gzieło1 · Krzysztof Janeczko1 · Władysław Węglarz3 · Krzysztof Jasiński3 · Krzysztof Kłodowski2 · Zuzanna Setkowicz1  Received: 20 January 2020 / Accepted: 2 July 2020 © The Author(s) 2020

Abstract To maintain its functional abilities, the mature brain obtains energy from glucose produced in carbohydrate metabolism. When carbohydrates are eliminated from the diet, the energy comes from the oxidation of fatty acids. In this metabolic state called ketosis, ketone bodies are formed: β-hydroxybutyric acid (bHb), acetone, and acetoacetate as alternative source of energy passing through the blood–brain barrier easily. The ketosis state can be achieved through various strategies like caloric restriction, supplementation with medium-chain triglycerides, intense physical training, or ketogenic diet (KD). Using KD, drug-resistant epilepsy has been successfully treated in children and adults. It can also exert neuroprotective influences in cases of brain damage, glioblastoma multiforme, and Alzheimer’s or Parkinson’s diseases. Although many possible mechanisms of KD activity have been proposed, newer hypotheses appear with the research progress, mostly characterizing the brain under pathological but not normal conditions. Since different pathological conditions may affect the mechanism of KD action differently, additional research on the normal brain appears reasonable. For this purpose, young adult rats were treated with 4-month-lasting KD. Then, MRI structural measurements, spectroscopy, and tractography were performed. The procedures revealed significant increases in the concentration of glutamine, glutamate, glutathione and NAA, accompanied by changes in the pattern of neuronal connections of the striatum and hippocampal formation. This implies a possible involvement of these structures in the functional changes occurring in the brain after KD application. Thus, the investigations on the normal brain add important details concerning mechanisms underlying KD effects without their possible modification by a pathological status. Keywords  Ketogenic diet · MRI spectroscopy · Normal rat · Tractography Abbreviations Acn Acetone Act Acetate Ala  l-Alanine ALP Alkaline phosphatase K. Gzieło and K. Janeczko contributed equally to this work. * Zuzanna Setkowicz zuzanna.setkowicz‑[email protected] 1



Department of Neuroanatomy, Faculty of Biology, Gronostajowa 9, 30‑387 Kraków, Poland

2



Faculty of Physics and Applied Computer Science, AGH University of Science and Technology, 30‑059 Kraków, Poland

3

Department of Magnetic Resonance Imaging, Institute of Nuclear Physics Polish Academy of Sciences, Radzikowskiego 152 St, 31‑342 Kraków, Poland



Asp Aspartate ATP Adenosine triphosphate bHb β-Hydroxybutyric acid CPK Creatine phosphokinase Cr Creatine FA Fractional anisotropy GABA γ-Aminobutyric acid GAD Glutamic acid decarboxylase GCL Glutamate cysteine ligase Glc Glucose Gln Glutamine Glu Gl