Article
Biochemistry & Molecular Biology
Young-Sun Kwon, Jin-Sung Ko, Se-Young Oh, Young Taek Han, Sangmee Ahn Jo
Summary: Alzheimer's disease (AD) is characterized by blood-brain barrier dysfunction. Our study focused on oleracones, a group of flavonoids isolated from Portulaca oleracea L. extract, which has anti-inflammatory and antioxidant effects. We found that oleracone F treatment improved memory dysfunction in AD model transgenic mice by reducing amyloid plaques, amyloid precursor protein levels, and inflammation in the brain. In vitro studies also showed that oleracones D, E, and F blocked the elevation of VCAM-1 protein induced by TNF-alpha, inhibiting leukocyte adhesion. Overall, oleracones ameliorated cognitive impairment by reducing leukocyte infiltration to the brain and modulating brain inflammation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Geriatrics & Gerontology
Lianne A. Hulshof, Leon A. Frajmund, Danny van Nuijs, Denise C. N. van der Heijden, Jinte Middeldorp, Elly M. Hol
Summary: Through a series of memory tests, the researchers determined that the Barnes maze task is better suited for studying subtle learning and memory deficits in 9-month-old APPswe/PS1dE9 mice. The test revealed deficits in spatial memory and cognitive flexibility in the APPswe/PS1dE9 mice compared to wildtype littermates. Additionally, there were no sex-dependent memory deficit differences in this AD mouse model at this age.
NEUROBIOLOGY OF AGING
(2022)
Article
Immunology
Anne-Laure Hemonnot-Girard, Audrey J. Valverde, Jennifer Hua, Charlene Delaygue, Nathalie Linck, Tangui Maurice, Francois Rassendren, Helene Hirbec
Summary: This study investigated the impact of CX3CR1 haplodeficiency on Alzheimer's disease pathology progression in a mouse model. The results showed that CX3CR1 deficiency had little effect on the pathology progression, but the APP(swe)/PSEN1(dE9):CX3CR1(+/eGFP) mouse line is a useful model for studying the role of microglia in Alzheimer's disease. Additionally, despite higher A beta plaque density in females, their glial reaction, inflammation status and memory deficits were not different from age-matched males.
BRAIN BEHAVIOR AND IMMUNITY
(2021)
Article
Biochemistry & Molecular Biology
Woo-In Ryu, Mariana K. Bormann, Minqi Shen, Dohoon Kim, Brent Forester, Yeongwon Park, Jisun So, Hyemyung Seo, Kai-C. Sonntag, Bruce M. Cohen
Summary: The study found that neural progenitor cells and astrocytes differentiated from induced pluripotent stem cells of late-onset Alzheimer's disease patients exhibit multiple inter-related bioenergetic alterations, including changes in mitochondrial respiration, reduced levels of NAD/NADH, and diminished glucose uptake. These findings suggest that Alzheimer's disease may involve multiple hits and innate inefficient cellular energy management.
MOLECULAR PSYCHIATRY
(2021)
Review
Biochemistry & Molecular Biology
Meiying Song, Xiang Fan
Summary: Elderly people over the age of 65 are most susceptible to Alzheimer's disease (AD), which is associated with apparent metabolic alterations. Currently, there is no cure for AD, and only a few drugs have been approved by the FDA to alleviate its symptoms. Numerous preclinical and clinical trials have investigated the impact of adjusting whole-body and intracellular metabolism on the development of AD. Recent evidence suggests that mitochondria play a crucial role by initiating a stress response, leading to healthy aging and neuroprotection. There is also growing awareness of the differential risk and potential targeting strategies related to metabolism and the microbiome. Mitochondrial bioenergetics, quality-control mechanisms, and mitochondrial-linked inflammatory responses are considered potential therapeutic targets for AD. This review summarizes and highlights these recent advancements.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Behavioral Sciences
Fran C. van Heusden, Sara Bonson, Oliver Stiedl, August B. Smit, Ronald E. van Kesteren
Summary: This study designed an automated figure-8-maze to test cognitive functioning in mice over a period of 4 months, finding that APP/PS1 mice did not show impaired delayed spatial alternation until 6 months of age under the current experimental conditions.
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2021)
Review
Immunology
Yun Li, Xiaohuan Xia, Yi Wang, Jialin C. Zheng
Summary: This review summarizes the latest progress on the relationship between mitochondrial dysfunction and microglial activation in AD, highlighting the importance of studying this relationship and potential therapeutic strategies.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Food Science & Technology
Min Wang, Tianxiong Xu, Li Gao, Chujun Huang, Piao Xu, Congcong Gong, William Kwame Amakye, Linfeng Liao, Maojin Yao, Jiaoyan Ren
Summary: Mitochondrial dysfunction is closely associated with aging and aging-related diseases, such as Alzheimer's disease. It is unclear if different mouse models with mitochondrial-related diseases exhibit similar changes in mitochondrial morphology in the same tissues. Additionally, it is unknown if similarities in mitochondrial morphology can be used as a marker for screening and discovering mitochondrial-protective substances.
FOOD SCIENCE AND HUMAN WELLNESS
(2023)
Review
Biochemistry & Molecular Biology
Janusz Wieslaw Blaszczyk
Summary: According to Alzheimer's Disease International, there are 55 million people worldwide living with dementia, which is a set of symptoms resulting from brain damage. The symptoms involve progressive impairments in memory, thinking, and behavior, often accompanied by emotional problems, language difficulties, and decreased motivation. Although attempts to treat dementia by addressing symptoms have failed, this narrative review aims to explain the etiology of dementia and Alzheimer's disease through the perspective of energy and cognitive metabolism dysfunction in an aging brain.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Andreia Faria-Pereira, Vanessa A. Morais
Summary: The brain is one of the most energy-consuming organs in the body, and synaptic transmission is a major contributor to this energy consumption. The brain primarily uses glucose for energy, which is metabolized through glycolysis and/or mitochondrial oxidative phosphorylation. This review examines the balance between glycolysis and oxidative phosphorylation in meeting synaptic energy demands. Dysregulation of synaptic bioenergetics is increasingly associated with neurodegenerative disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Ankit Verma, Anna Shteinfer-Kuzmine, Nikita Kamenetsky, Srinivas Pittala, Avijit Paul, Edna Nahon Crystal, Alberto Ouro, Vered Chalifa-Caspi, Swaroop Kumar Pandey, Alon Monsengo, Noga Vardi, Shira Knafo, Varda Shoshan-Barmatz
Summary: Alzheimer's disease (AD) is associated with mitochondrial dysfunctions, and VDAC1 plays a key role in controlling metabolism and calcium homeostasis. This study used a newly developed inhibitor, VBIT-4, to target VDAC1 and prevent mitochondrial dysfunction and cell death.
TRANSLATIONAL NEURODEGENERATION
(2022)
Article
Cell Biology
Konstantinos Palikaras, Kavya Achanta, Seoyun Choi, Mansour Akbari, Vilhelm A. Bohr
Summary: Evidence suggests that mitochondrial dysfunction precedes tau aggregation in tauopathies, impacting neuronal homeostasis and mobility in animals. Understanding the early molecular mechanisms of mitochondrial dysfunction in tauopathy holds significant clinical and therapeutic value.
Article
Biochemistry & Molecular Biology
Moritz A. Niederschweiberer, Patrick M. Schaefer, Larry N. Singh, Ludwig Lausser, Devyani Bhosale, Raphael Hesse, Enrico Calzia, Hans A. Kestler, Angelika Rueck, Douglas C. Wallace, Bjoern von Einem, Christine A. F. von Arnim
Summary: Alzheimer's disease affects over 30 million people globally and mitochondrial dysfunction plays a significant role in its development. However, the selective vulnerability and associated mitochondrial dysfunction remain unresolved.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Mariana Yolotzin Garcia-Bermudez, Rupali Vohra, Kristine Freude, Peter van Wijngaardenan, Keith Martin, Maj Schneider Thomsen, Blanca Irene Aldana, Miriam Kolko
Summary: This review discusses the diagnostic challenges of Alzheimer's disease (AD) and emphasizes the potential of using retinal alterations as early indicators. It highlights the complexity introduced by the similarities shared with other retinal diseases in the search for AD-specific markers. The review provides a comprehensive overview of the current landscape in AD diagnosis and highlights avenues for progress through retinal examination.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Neurosciences
Jiayi Song, Xuehan Yang, Ming Zhang, Chunyan Wang, Li Chen
Summary: Glutamate plays a crucial role in Alzheimer's disease, not only related to excitotoxicity but also to metabolic balance disorder. Maintaining the balance of glutamate metabolism in the brain is essential for central nervous system health, with mitochondrial glutamate metabolism being a potential target for Alzheimer's disease treatment.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Cell Biology
Anna Luna Molgaard Tams, Berta Sanz-Morello, Emil Winther Westi, Zaynab Ahmad Mouhammad, Jens Velde Andersen, Kristine Karla Freude, Rupali Vohra, Jens Hannibal, Blanca Irene Aldana, Miriam Kolko
Summary: Visual changes are among the earliest symptoms observed in patients with Alzheimer's disease (AD). Research has shown that there are pathophysiological processes occurring in the retina of AD patients and animal models, including amyloid-beta plaque formation, vascular changes, neuroinflammation, and loss of retinal ganglion cells. Studies on the 5xFAD mouse model have revealed that there may be metabolic alterations in the retina of AD, which could impact the activity and survival of retinal ganglion cells.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2022)
Editorial Material
Biochemistry & Molecular Biology
Sandra Krull, Ana Aranda Silva, Dariya Afanasyeva, Sofie Christensen, Marta Agostinho
Summary: Postdocs are at a challenging stage in their career progression, and research organisations could offer more support to help them succeed.
Article
Endocrinology & Metabolism
Laura M. McNair, Graeme F. Mason, Golam M. Chowdhury, Lihong Jiang, Xiaoxian Ma, Douglas L. Rothman, Helle S. Waagepetersen, Kevin L. Behar
Summary: Anaplerosis, mediated by pyruvate carboxylase (PC) in astroglia, varies across different brain regions. The rate of PC contributes to oxidative glucose consumption and is positively correlated with glutamate/glutamine cycling.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2022)
Article
Biochemical Research Methods
Michael Sorensen, Anne Byriel Walls, Gitte Dam, Lasse Kristoffer Bak, Jens Velde Andersen, Peter Ott, Hendrik Vilstrup, Arne Schousboe
Summary: Hepatic encephalopathy is a neuropsychiatric complication of liver failure, characterized by reduced brain energy metabolism. This reduction is likely caused by elevated GABA levels due to increased synthesis of glutamine in astrocytes for ammonia detoxification.
ANALYTICAL BIOCHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Mirolyuba Ilieva, Blanca Irene Aldana, Kasper Tore Vinten, Sonja Hohmann, Thomas William Woofenden, Renate Lukjanska, Helle S. Waagepetersen, Tanja Maria Michel
Summary: The remodeling of brain morphology and proteome during embryonic development, along with its connection to cellular metabolism, could be crucial in understanding the pathological mechanisms of certain neurodevelopmental disorders. Cerebral organoids derived from autism spectrum disorder (ASD) patients were used to capture key moments in neuronal development and investigate metabolism and protein expression. The early stages of development, particularly when neurogenesis begins, were found to be critical in ASD pathogenesis. Differences in energy metabolism and proteome were observed, including increased glycolysis, decreased ATP production, and altered expression of cell adhesion proteins, cell cycle regulators, cytoskeletal proteins, and transcription factors. Furthermore, a cluster analysis based on differential protein expression identified potential biomarkers that could be explored for drug development.
MOLECULAR PSYCHIATRY
(2022)
Article
Neurosciences
Maria Hvidberg Petersen, Cecilie Wennemoes Willert, Jens Velde Andersen, Mette Madsen, Helle Sonderby Waagepetersen, Niels Henning Skotte, Anne Norremolle
Summary: This study reveals that synaptic mitochondria in the striatum are more severely affected by Huntington's disease pathology than those in the cortex, leading to increased oxygen consumption and mitochondrial proton leak of striatal synaptosomes.
JOURNAL OF HUNTINGTONS DISEASE
(2022)
Article
Neurosciences
Emil W. Westi, Emil Jakobsen, Caroline M. Voss, Lasse K. Bak, Lars H. Pinborg, Blanca Aldana, Jens Andersen
Summary: Differences in cellular composition and structure may influence the metabolism of rodent and human brain. Human cerebral slices have lower metabolic rates but higher coupled respiration and more efficient mitochondrial coupling compared to mouse slices.
MOLECULAR NEUROBIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Jens Andersen, Arne Schousboe
Summary: Glutamine plays an essential role in cerebral metabolism, including ammonia homeostasis, energy metabolism, and neurotransmitter recycling. The balance of cerebral glutamine is regulated by the metabolic coupling of neurons and astrocytes, and disruptions in this balance are associated with various neurological diseases. Decreased astrocyte glutamine synthesis can lead to a deficiency in metabolic substrates and precursors for neurotransmitter synthesis in neurons, resulting in synaptic dysfunction.
NEUROCHEMICAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Jens Andersen, Emil W. Westi, Elliott S. Neal, Blanca Aldana, Karin Borges
Summary: Ketogenic diets and medium-chain triglycerides play important roles in the treatment of neurological disorders, with their metabolites serving as auxiliary brain fuels in different cell types without notable competition.
NEUROCHEMICAL RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Jens V. Andersen, Arne Schousboe, Petrine Wellendorph
Summary: Synaptic regulation of GABA, the primary inhibitory neurotransmitter, is crucial for brain function. Astrocytes play fundamental roles in regulating synaptic GABA signaling by removing excess GABA from the synapse and using it as a metabolic substrate for glutamine synthesis. The flow of GABA and glutamine between neurons and astrocytes, known as the GABA-glutamine cycle, is essential for maintaining inhibitory signaling.
ESSAYS IN BIOCHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Jens V. Andersen, Arne Schousboe
Summary: Since the recognition of glutamate and GABA as principal neurotransmitters, significant discoveries have been made about their synaptic homeostasis. The glutamate/GABA-glutamine cycle, involving the recycling between neurons and astrocytes, plays a crucial role in maintaining synaptic transmission. The metabolic function of neurons and astrocytes is closely related to the glutamate/GABA-glutamine cycle, with astrocytes providing metabolic support for neurons. The review focuses on cellular uptake, metabolism, and recycling of glutamate and GABA, as well as their role in brain pathology and the potential of targeting astrocyte metabolism for intervention.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Jens V. Andersen, Emil W. Westi, Nane Griem-Krey, Niels H. Skotte, Arne Schousboe, Blanca I. Aldana, Petrine Wellendorph
Summary: This study investigated the role of CaMKIIa in brain energy and neurotransmitter metabolism using a genetic knockout mouse model. The results showed that the oxidative metabolism of glucose in the cerebral cortex was significantly reduced in the absence of CaMKIIa, while the metabolism of acetate, primarily reflecting astrocyte metabolism, was unaffected. Additionally, the metabolism of glutamate in the excitatory system was impaired, while the metabolism of GABA was unaffected. These findings suggest that CaMKIIa signaling plays a metabolic role in cellular energy and neurotransmitter metabolism in the brain.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Neurosciences
Emil W. Westi, Jens Andersen, Blanca I. Aldana
Summary: Disrupted brain metabolism is crucial for neurodegenerative diseases, and the energy metabolism of neurons and astrocytes through the glutamate/GABA-glutamine cycle plays a vital role in neurotransmitter recycling. Isotope tracing, a technique to monitor cellular metabolism, has helped elucidate the mechanistic involvement of altered brain metabolism in disease progression. This review discusses the advantages, drawbacks, and applications of isotope tracing in different cerebral preparations and narrates how it has facilitated the discovery of central metabolic features in neurodegeneration, particularly in the metabolic cooperation between neurons and astrocytes.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Laura Mikel Mcnair, Jens Velde Andersen, Helle Sonderby Waagepetersen
Summary: This study reveals fundamental alterations in cellular energy and neurotransmitter metabolism in the aging brain, which may contribute to age-related hippocampal deficits.
NEUROCHEMISTRY INTERNATIONAL
(2023)