Review
Nutrition & Dietetics
Lian Wang, Peijie Chen, Weihua Xiao
Summary: Beta-hydroxybutyrate (beta-HB) is an important ketone body that serves as both an energy source to maintain metabolic homeostasis and a signaling molecule with epigenetic regulatory functions to delay age-related diseases. Research supports the effectiveness of endogenous beta-HB administration or exogenous supplementation as strategies to induce nutritional ketosis.
Article
Multidisciplinary Sciences
A. M. Whipp, E. Vuoksimaa, T. Korhonen, R. Pool, A. But, L. Ligthart, F. A. Hagenbeek, M. Bartels, L. H. Bogl, L. Pulkkinen, R. J. Rose, D. Boomsma, J. Kaprio
Summary: Human aggression is a complex behavior with poorly understood biological underpinnings. A study found that only one low-molecular-weight metabolite, 3-hydroxybutyrate, showed a significant negative association with aggression, suggesting a potential role of ketone metabolism in aggression. Further research is warranted to explore this relationship.
SCIENTIFIC REPORTS
(2021)
Review
Biotechnology & Applied Microbiology
Aliya Yao, Zihua Li, Jinyan Lyu, Liusong Yu, Situ Wei, Lingyun Xue, Hui Wang, Guo-Qiang Chen
Summary: D-3HB, a natural ketone body, has beneficial effects on physical and metabolic health. Biologically synthesized D-3HB can increase plasma D-3HB levels faster than traditional methods. Its applications include improving exercise performance and treating metabolic or age-related diseases.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2021)
Article
Sport Sciences
Naoki Horii, Eri Miyamoto-Mikami, Shumpei Fujie, Masataka Uchida, Kenichiro Inoue, Keiko Iemitsu, Izumi Tabata, Shigeru Nakamura, Jun Tsubota, Kazuo Tsubota, Motoyuki Iemitsu
Summary: The effects of acute beta-HB supplementation on exercise performance were assessed in rats. The results suggest that acute beta-HB salt administration may accelerate high-intensity intermittent exercise (HIIE) and resistance exercise (RE) performance, and the changes in metabolic responses in skeletal muscle may be involved in the enhancement of HIIE performance.
MEDICINE & SCIENCE IN SPORTS & EXERCISE
(2023)
Article
Biochemistry & Molecular Biology
Lee-Way Jin, Jacopo Di Lucente, Ulises Ruiz Mendiola, Nopparat Suthprasertporn, Alexey Tomilov, Gino Cortopassi, Kyoungmi Kim, Jon J. Ramsey, Izumi Maezawa
Summary: This study investigated the impact of BHB on AβO-stimulated hiMG and found that BHB can mitigate inflammation and mitochondrial damage caused by AβO, rectify MKP, and restore cellular function. The authors suggest that these effects of BHB may contribute to the therapeutic benefits of ketogenic diet intervention in aged mice and individuals with mild AD.
Article
Medicine, Research & Experimental
Ke Li, Wen-hong Wang, Jia-bin Wu, Wei-hua Xiao
Summary: ss-Hydroxybutyrate (ss-HB), the most abundant ketone body, serves as an alternative energy fuel, providing energy to extrahepatic tissues during hypoglycemia or glycogen depletion. Intensive research has revealed the roles of ss-HB as a signal molecule and epigenetic regulatory factor. Due to its ability to regulate various physiological and pathological processes, ss-HB holds potential as a therapeutic for metabolic diseases, particularly liver disorders. This review summarizes the therapeutic effects of ss-HB on liver diseases and explores the potential of exogenous and endogenous ketosis as adjuvant nutritional therapies.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Victoire Gouirand, Tristan Gicquel, Evan C. Lien, Emilie Jaune-Pons, Quentin Da Costa, Pascal Finetti, Elodie Metay, Camille Duluc, Jared R. Mayers, Stephane Audebert, Luc Camoin, Laurence Borge, Marion Rubis, Julie Leca, Jeremy Nigri, Francois Bertucci, Nelson Dusetti, Juan Lucio Iovanna, Richard Tomasini, Ghislain Bidaut, Fabienne Guillaumond, Matthew G. Vander Heiden, Sophie Vasseur
Summary: Pancreatic ductal adenocarcinoma cells can activate ketone body metabolism using beta-hydroxybutyrate (beta OHB) as a fuel, which promotes PDA growth and progression. HMGCL, involved in ketogenesis, is found to be deregulated in PDA and its depletion impairs PDA migration and invasiveness. Disrupting HMGCL decreases PDA tumor growth, while beta OHB stimulates metastatic dissemination to the liver.
Article
Biochemistry & Molecular Biology
Hyeonwi Son, Ji Hyeong Baek, Jae Soon Kang, Soonwoong Jung, Hye Jin Chung, Hyun Joon Kim
Summary: The study identified an increase in beta-hydroxybutyrate (BHB) levels in the prefrontal cortex during acute stress, suggesting a potential role of BHB metabolism in acute stress responses. Additionally, metabolic enzymes related to BHB utilization were found to increase in the prefrontal cortex, influencing neurotransmitter levels and behavior under stress conditions.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Medicine, General & Internal
David J. Dearlove, David Holdsworth, Tom Kirk, Leanne Hodson, Evelina Charidemou, Eline Kvalheim, Brianna Stubbs, Andrew Beevers, Julian L. Griffin, Rhys Evans, Jeremy Robertson, Kieran Clarke, Pete J. Cox
Summary: This study investigated ketone oxidation rates in athletes under metabolic conditions of high and low carbohydrate and fat availability. The findings suggest that low CHO availability may modestly impair beta HB oxidation rates during exercise.
FRONTIERS IN MEDICINE
(2021)
Review
Neurosciences
Dongting Tian, Shin-Ichi Izumi
Summary: Understanding cortical circuits is crucial in neuroscience and neurorehabilitation. Transcranial magnetic stimulation (TMS) allows non-invasive probing of neuronal activity. This review integrates evidence from neurocytology and neurophysiology to elucidate the relationship between microscopic neuronal landscape and macroscopic TMS outcome. A preliminary neuronal model of the human motor cortex is proposed, linking TMS mechanisms with neuronal activity.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Endocrinology & Metabolism
Minyoung Lee, Yongin Cho, Yong-ho Lee, Eun Seok Kang, Bong-soo Cha, Byung-Wan Lee
Summary: This study investigated the clinical relevance of ketone bodies in newly diagnosed type 2 diabetes patients. The results showed that patients with higher initial serum β-hydroxybutyrate (BHB) levels had greater improvement in glycemic control after 6 months of anti-diabetic treatment, as indicated by lower HbA1c levels and better blood sugar control.
DIABETES & METABOLISM
(2023)
Article
Chemistry, Multidisciplinary
Hiroki Kondou, Risa Bandou, Hiroaki Ichioka, Ryota Matsunari, Masataka Kawamoto, Nozomi Idota, Deng Ting, Satoko Kimura, Hiroshi Ikegaya
Summary: Ketoacidosis is a common disease that may result in death, and measuring BHB levels in forensic autopsies can help diagnose it as a cause of death. However, increased BHB values are not always indicative of ketoacidosis, as other factors like PMI can also affect BHB levels. Results suggest that BHB values may increase after death, highlighting the importance of considering PMI in diagnosing ketoacidosis.
APPLIED SCIENCES-BASEL
(2022)
Article
Biology
Ross T. Lindsay, Sophie Dieckmann, Dominika Krzyzanska, Dominic Manetta-Jones, James A. West, Cecilia Castro, Julian L. Griffin, Andrew J. Murray
Summary: Under conditions of low-flow ischemia, the heart can generate ketones through pathways involving HMGCS2 and SCOT, impacting cardiac functional recovery.
Article
Obstetrics & Gynecology
Emma G. Whatley, Thi T. Truong, Dagmar Wilhelm, Alexandra J. Harvey, David K. Gardner
Summary: Exposure to the ketone beta-hydroxybutyrate (beta OHB) impairs preimplantation mouse embryo development, metabolism, epigenetics, and post-transfer viability, with significant effects seen at ketogenic diet (KD)-relevant serum concentrations. These findings suggest a potential detrimental impact on embryo development and viability due to maternal diets that elevate beta OHB levels.
HUMAN REPRODUCTION
(2022)
Article
Biochemistry & Molecular Biology
Jin Chen, Zihua Li, Yudian Zhang, Xu Zhang, Shujie Zhang, Zonghan Liu, Huimei Yuan, Xiangsheng Pang, Yaxuan Liu, Wuchen Tao, Xiaoping Chen, Peng Zhang, Guo-Qiang Chen
Summary: This study investigates the therapeutic effects of (D)-3-hydroxybutyrate (3HB) on muscle atrophy induced by hindlimb unloading. The results show that 3HB maintains the balance of muscle protein synthesis and degradation through the Akt/FoxO3a and mTOR/4E-BP1 pathways. It also regulates protein homeostasis and metabolism through various pathways. Additionally, 3HB decreases purine degradation and increases glutamate accumulation, providing evidence for its effectiveness in treating muscle atrophy.
CELL AND BIOSCIENCE
(2022)
Article
Cardiac & Cardiovascular Systems
Mahmoud Diab, Rita Musleh, Thomas Lehmann, Christoph Sponholz, Mathias W. Pletz, Marcus Franz, P. Christian Schulze, Otto W. Witte, Klaus Kirchhof, Torsten Doenst, Albrecht Gunther
Summary: The study found that pre-ICH is not an independent predictor for postoperative neurological deterioration or hospital mortality in patients with IE, but postoperative coagulation management is crucial. Additional randomized clinical trials are needed to confirm these conclusions due to the limited number of patients with pre-ICH in this study.
EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY
(2021)
Article
Cell Biology
Lei Cao-Lei, Marion I. van den Heuvel, Klaus Huse, Matthias Platzer, Guillaume Elgbeili, Marijke A. K. A. Braeken, Renee A. Otte, Otto W. Witte, Matthias Schwab, Bea R. H. van den Bergh
Summary: Epigenetic changes related to altered behavior and neuropsychiatric disorders are associated with maternal anxiety during pregnancy. The study found a link between maternal anxiety and children's DNA methylation levels, with sex differences and timing effects being highly important. However, DNA methylation was not supported as the underlying mechanism for the impact of maternal anxiety during pregnancy on offspring's behavioral measures.
Article
Neurosciences
Mina Kheirkhah, Philipp Baumbach, Lutz Leistritz, Otto W. Witte, Martin Walter, Jessica R. Gilbert, Carlos A. Zarate, Carsten M. Klingner
Summary: This study using MEG and bootstrapping method found that the greatest differences in brain response to high-arousing emotional and neutral stimuli occur in the right temporo-parietal region. This highlights the essential role of the right hemisphere in emotion processing.
Editorial Material
Physiology
Knut Kirmse
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yuanyuan Ji, Dennis Koch, Jule Gonzalez Delgado, Madlen Guenther, Otto W. Witte, Michael M. Kessels, Christiane Frahm, Britta Qualmann
Summary: Ischemic stroke in mice leads to a decline in dendritic arborization of penumbral neurons, which is repaired by the actin nucleator Cobl. The decreased Cobl levels caused by stroke and excitotoxicity are rapidly restored by increased mRNA expression, playing a pivotal role in dendritic arbor repair poststroke. Cobl knockout mice show impaired dendritic repair poststroke, highlighting the crucial role of Cobl in poststroke recovery.
Article
Medicine, General & Internal
Mahmoud Diab, Marcus Franz, Stefan Hagel, Albrecht Guenther, Antonio Struve, Rita Musleh, Anika Penzel, Christoph Sponholz, Thomas Lehmann, Henning Kuehn, Karim Ibrahim, Marcus Jahnecke, Holger Sigusch, Henning Ebelt, Gloria Faerber, Otto W. Witte, Bettina Loeffler, Michael Bauer, Mathias W. Pletz, P. Christian Schulze, Torsten Doenst
Summary: Establishing an endocarditis network led to earlier referral of patients with fewer pre-operative complications. Adherence to recommendations of the endocarditis team was associated with lower post-operative stroke and in-hospital mortality, as well as improved 5-year survival rates.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Cell Biology
Marie-Luise Ederer, Madlen Guenther, Lena Best, Julia Lindner, Christoph Kaleta, Otto W. Witte, Rowena Simon, Christiane Frahm
Summary: Inflammation is believed to play a role in cognitive decline during aging. This study examines the impact of physical activity and social isolation on cognitive function and inflammation in old mice. The results show that voluntary wheel running improves cognitive function, while social isolation has negative effects. Inflammatory markers increase in both the hippocampus and colon during aging, and voluntary wheel running specifically attenuates intestinal inflammation.
Article
Cell Biology
Diana M. Morales-Prieto, Jose M. Murrieta-Coxca, Milan Stojiljkovic, Celia Diezel, Priska E. Streicher, Julian A. Henao-Restrepo, Franziska Roestel, Julia Lindner, Otto W. Witte, Sebastian Weis, Christian Schmeer, Manja Marz
Summary: Extracellular vesicles, specifically small EVs, are involved in neuroinflammation and neurodegenerative diseases. Aging brains show increased neuroinflammation and glial activation, which can be influenced by EVs. Our study demonstrates that sEVs from aged mice can cross the blood-brain barrier and induce glial cell activation in young animals.
Article
Biochemistry & Molecular Biology
Quratul Ain, Christian W. Schmeer, Diane Wengerodt, Yvonne Hofmann, Otto W. Witte, Alexandra Kretz
Summary: This article presents a practical workflow for the efficient purification of viable neural cells from the mature CNS. The protocol is suitable for acquiring and phenomapping CNS neural cells at different states, including health, physiological and precocious aging, and genetically provoked neurodegeneration. It is a rapid and efficient method that preserves physiological cell proportions and can be applied in various downstream applications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Knut Kirmse, Chuanqiang Zhang
Summary: GABAergic signaling plays a crucial role in the inhibitory stabilization and coordination of excitatory neurons in mature cortical circuits. This review examines how GABA-releasing interneurons acquire their network functions during development, focusing on the visual neocortex and hippocampus in mice and rats. The authors propose that inhibitory stabilization is not functional at the onset of patterned activity, and that glutamatergic neurons are stable by themselves. The strengthening of inhibitory synaptic transmission toward eye opening shapes cortical network dynamics and allows the developing cortex to disengage from extra-cortical synaptic drive. The framework presented in this review has implications for our understanding of human cortical development and the treatment of neonatal seizures.
Review
Cardiac & Cardiovascular Systems
Rita Musleh, Peter Schlattmann, Tulio Caldonazo, Hristo Kirov, Otto W. Witte, Torsten Doenst, Albrecht Guenther, Mahmoud Diab
Summary: This study aimed to evaluate the impact of early surgery on postoperative neurological deterioration and all-cause mortality in patients with infective endocarditis (IE) and intracranial hemorrhage (ICH). The results showed that early surgery was associated with a higher risk of neurological deterioration but not with higher mortality. The 30-day mortality in patients who were denied surgery needs further investigation.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2022)
Article
Biology
Juergen Graf, Vahid Rahmati, Myrtill Majoros, Otto W. Witte, Christian Geis, Stefan J. Kiebel, Knut Holthoff, Knut Kirmse
Summary: Spontaneous correlated activity is a common characteristic of immature neural circuits. However, little is known about the cellular dynamics and intrinsic mechanisms underlying network burstiness. By mapping the developmental trajectories of spontaneous network activity in the hippocampal area CA1 of mice, it was found that network burstiness peaks in the second postnatal week, reflecting an increased functional coupling of individual neurons to local population activity. However, pairwise neuronal correlations are low, and network bursts recruit CA1 pyramidal cells in a virtually random manner.
Article
Cell Biology
Silvio Schmidt, Madlen Haase, Lena Best, Marco Groth, Julia Lindner, Otto W. Witte, Christoph Kaleta, Christiane Frahm
Summary: Research has shown that late-onset environmental enrichment (EE) can improve cognitive abilities and affect gene expression in the hippocampus of old mice. The positive cognitive effects were reflected by specific changes in the hippocampal transcriptome, with late-onset EE having a greater impact on transcription than age. Some genes that play a role in dendritic spine plasticity and age-related molecular signaling cascades were counter-regulated by late-onset EE. These findings suggest that EE is a promising non-pharmacological intervention against cognitive decline.
Article
Cell Biology
Sidra Gull, Christian Gaser, Karl-Heinz Herrmann, Anja Urbach, Marcus Boehme, Samia Afzal, Juergen R. Reichenbach, Otto W. Witte, Silvio Schmidt
Summary: By using MRI and DBM, we examined the structural changes in the brains of male RccHan:WIST rats. The study found that the overall brain volume increased with age, but there were also divergent local morphologic alterations. The visual, auditory, and somatosensory cortical areas showed shrinkage, while the higher-order brain areas such as the ectorhinal, entorhinal, retrosplenial, and cingulate cortical regions were preserved and grew with age.
Article
Neurosciences
Robert Steinbach, Nayana Gaur, Annekathrin Roediger, Thomas E. Mayer, Otto W. Witte, Tino Prell, Julian Grosskreutz
Summary: This study used the novel D50 model to investigate correlations between diffusion tensor imaging measures and ALS pathology. High disease aggressiveness patients showed specific white matter pathway abnormalities, and there were correlations between disease accumulation and DTI measures, especially in the early stages of the disease.
HUMAN BRAIN MAPPING
(2021)