Energy metabolism and cognitive function -
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CMR glc is the cerebral metabolic rate of glucose and is usually determined together with the apparent maximum transport T max and the apparent Michaelis constant of glucose transport K t using labeling of plasma and brain glucose Duarte et al.
In glial cells, GLS is neglected because the net 13 C labeling follows the direction of glutamine synthesis.
V ex can exchange with unlabeled glutamine of undefined origin Oz et al. Besides the contribution to amino acid synthesis, V PC also represents glutamine efflux V efflux from the brain i. Glutamate oxidation in the model is possible through V X composite representation of AST and GDH.
Note that both V Gln and V NT represent the glutamate-glutamine cycle. One is rather used in the one-compartment model V Gln as an exchange rate between glutamate and glutamine, while the other in the two-compartment model V NT.
Labeling of a particular nucleus depends on pool size and the numbers of upstream and downstream fluxes Henry et al. Glutamate is the most concentrated amino acid observed by 13 C MRS Figure 4. Glutamate labeling depends on both V TCA and V X , meaning that these two fluxes play an important role in defining glutamate turnover.
While glutamate C4 relies on the composite flux V gt , that is V X. Therefore, the information concerning V X is mainly stored in the initial slopes of the turnover curves of position C4, C3, and C2 of glutamate for V X n and glutamine for V X g. In the special case of V X g , this flux is particularly difficult to estimate, because labeled molecules from the glial TCA cycle into glial glutamate can also be transferred via V PC Figure 2.
The value of V X has been matter of debate for a long time, as it has been considered by some to be much larger than V TCA Mason et al. Figure 4. Typical 13 C MRS spectra acquired in vivo in the rat brain during [1,6- 13 C 2 ]glucose infusion at Panel A shows a time course of 13 C labeling with a temporal resolution of 5.
The spectrum in B was acquired for 1. Panel C is an expansion of B depicting multiplets originated from isotopomers of glutamine Gln , glutamate Glu and aspartate Asp.
The neurotransmission rate, V NT , represents the conversion of glutamate to glutamine and vice versa. In this process the carbon positions are maintained. Therefore, V NT mostly depends on the relative steady-state enrichment of the turnover curves of glutamate and glutamine: the closer they are to each other, the faster V NT.
The first turn of the TCA cycle results in label transfer from glucose to glutamate via V X. Usually glutamate C4 is the first detectable peak in a spectrum during an experiment, as it appears within the first 5 min of infusion Patel et al. Then, in the subsequent TCA cycle label is transferred from position C4 to C3 and C2.
In neurons, V PDH will therefore rely on the slope and the steady-state enrichment of the turnover curves of position C4, C3, and C2 of glutamate and glutamine, as labeling from glutamate is transferred to glutamine. As aspartate is mainly labeled via transamination of the TCA cycle intermediate oxaloacetate, the slope and the steady-state enrichment of position C3 and C2 of aspartate are further affected by V PDH.
The slopes of the labeling curves reflect, the rate of V PDH. In glia the situation is different, since label dilution due to V PC can occur. V PC dilutes position C3 and labels position C2 of glutamate and glutamine. Therefore, fast V g results in a relatively high and steep glutamine C3 turnover curve V g has to be fast to counterbalance the loss due to V PC.
Diluting position C3 and labeling position C2 of glutamate and glutamine, the measurement of V PC relies on the relative curves of position C3 and C2 of glutamate and glutamine, and the assumption that glutamate is mainly neuronal and glutamine mainly glial.
High C3 and low C2 labeling is associated with slow V PC , while high C2 and low C3 labeling reflect rather increased V PC. As mentioned above, V dil reflects dilution of the acetyl-CoA pool with specific unlabeled glial substrates.
Notably, V dil dilutes glial acetyl-CoA 13 C labeling relative to its precursor pyruvate. As the position C4 of glutamate and glutamine only receives labeling from acetyl-CoA, dilution at this point would lead to a lower steady-state C4 labeling. Since glutamate and glutamine are mainly present in neurons and glia, respectively, V dil is also responsible for lower FE of position C4, C3, and C2 of glutamine compared to glutamate.
However, the effect of V dil on enhancing the labeling difference between glutamate and glutamine is counteracted by V NT , which represents the glutamate-glutamine cycle. The faster the rate of V NT , the more similar will be the labeling of glutamate and glutamine.
Note that V dil in glial acetyl-CoA can result in glutamine C2 being similar or larger than glutamine C4, which has been observed in some studies discussed in Duarte et al. V ex represents an exchange between two putative glutamine pools, one of which is not released to neurons and may account for a continuous slow increase in FE over time Duarte and Gruetter, V ex can be in exchange with a 1 H MR invisible but 13 C labeled glutamine pool Hancu and Port, or with unlabeled amino acids from the blood i.
This second glutamine pool could be associated with biosynthetic pathways, which have rates much slower than mitochondrial energy metabolism McKenna, The effect of V ex is in practice observable near the end of an experiment, when the labeling of glutamine still increases, while glutamate is at steady-state.
Therefore, if mitochondrial metabolism is faster than glycolysis, oxidation of additional substrates, such as lactate, must occur under certain conditions Sonnay et al. In resting human brain, however, the brain exports lactate to the blood stream discussed in Dienel, The above descriptions are purely indicative of what happens for each flux independently.
Experimental data is a linear combination of many fluxes, which will adjust during fitting process to best describe the turnover curves. The first 13 C MRS data acquired in vivo upon stimulus-induced brain activity were modeled using a one-compartment model and reported a marked increase in total TCA cycle activity in the somatosensory cortex of stimulated rats compared to rest Hyder et al.
The following experiment consisted on measuring neuronal CMR glc ox under three different anesthesia-induced activity states, namely pentobarbital deep , α-chloralose moderate and morphine light Sibson et al.
According to this model, no stimulation of oxidative metabolism should occur in glia, in contrast to neurons. Later several studies in rat brain Patel et al. However, it should be noted that constraining the value of V PC to V GS and V TCA g to the total V TCA implies an effective coupling between glial oxidative metabolism and neuronal function.
Indeed, the astrocytic processes engulfing synapses are capable of sensing increased synaptic activity Iadecola and Nedergaard, ; Cheung et al. The 13 C MRS study by Gruetter et al. Using a similar model, glial oxidation and pyruvate carboxylase activity was shown to significantly contribute also to total glucose oxidation in awake animals Oz et al.
Recently, our group further addressed the issue of glial and neuronal oxidative metabolism coupled to neuronal activity. In particular, we first measured the cortical changes in metabolic fluxes induced by electrical stimulation of the four paws of rats.
We observed a similar increase in absolute terms of both glial and neuronal oxidative metabolism resulting from the increase in glutamate-glutamine cycle rate Figure 5 ; Sonnay et al.
Interestingly in this study, as well as in Patel et al. Indeed Patel and Tilghman reported that glutamate can stimulate pyruvate carboxylation Patel and Tilghman, Instead, glutamate could be oxidized in astrocytes to compensate for the high cost of glutamate uptake during neurotransmission McKenna, Figure 5.
Relation of estimated total, neuronal and glial glucose oxidative metabolism to the glutamate-glutamine cycle in the rat cortex anesthetized with α-chloralose originally reported in Sonnay et al.
Average fluxes across the resting in blue and stimulated in red group are shown with associated SD. In the study by Sonnay et al.
However, the simulations by DiNuzzo et al. are still unable to account for substantial V TCA g in cases of low glutamate-glutamine cycle rate. To summarize, in addition to the proposed coupling of neuronal oxidative metabolism and neurotransmission, astrocytes increase their oxidative metabolism too, resulting in a large production of ATP.
It is, therefore, important to investigate the exact fate of the ATP produced. In this context, the ATP produced in glia might notably support blood flow regulation Zonta et al. Glycogenolysis might moreover provide energy to support neurotransmission i. Brain vasculature is rich in arterioles and fine capillaries Reina-De La Torre et al.
In this context astrocytes and neurons are presumed to play a key role in modulating CBF to match energy demands. In astrocytes, activation of mGluR by glutamate triggers the translocation of the α-subunit of the receptors to phospholipase C PLC mediating the conversion of GTP to GDP Bockaert et al.
In neurons, cyclooxygenase COX converts AA into prostaglandins E 2 PGE 2 leading to vessel dilation Wang et al. In astrocytes, AA can be converted either to PGE 2 by COX Zonta et al. If AA is converted into hydroxyeicosatetraenoic acid HETE by ω-hydroxylase in pericytes, it will cause vasoconstriction Metea and Newman, New line of evidence suggest moreover that the astrocytic production of PGE 2 might be dependent on glutathione levels Howarth et al.
In neurons activation of ionotropic glutamate receptors located on the post-synaptic zone i. Interaction of NO with soluble guanylate cyclase sGC triggers cGMP dependent vasodilation mechanisms Laranjinha et al.
Intracellular adenosine can be released extracellularly by nucleoside transporters Iliff et al. Increase in cAMP leads to vasodilation and inhibits the vasoconstrictive effects of HETE Koehler et al. Figure 6. Schematic representation of possible signaling pathways mediating neurovascular coupling.
Arachidonic acid AA is then produced by phospholipase A 2 PLA 2. In astrocytes AA can be converted either to prostaglandins E 2 PGE 2 by cyclooxygenase COX or to epoxeicosatrienoic acids EET by epoxygenase for vasodilation.
If AA is converted into hydroxyeicosatetraenoic acid HETE by ω-hydroxylase, it will lead to vasoconstriction. In pericytes and smooth muscle cells NO interacts with the soluble guanylate cyclase sGC for cGMP- dependent vasodilation mechanisms.
Intracellular adenosine can be transported by the nucleoside transporters to activate the adenosine receptors AR for cAMP-dependent vasodilation mechanisms via adenylate cyclase and inhibiting the vasoconstrictive effects of HETE. Lactate can inhibit the astrocytic prostaglandin transporter PGT -mediated PGE-lactate exchange, increasing therefore extracellular PGE 2 concentration.
Astrocytes can modulate synaptic plasticity in releasing vesicles containing glutamate, D-serine, ATP and neurotrophic factors in an ATP-dependent manner.
Glutathione is produced in astrocytes and can be released through multidrug resistance proteins MRP mediating ATP hydrolysis. Release of ascorbate mediate non-hydrolytic ATP binding to volume-sensitive organic osmolyte-anion channel VSOAC and is stimulated by glutamate.
The dashed line represents vasodilation and the dotted line vasoconstriction. Local CBF response could be immediately regulated by fast ms feed-forward mechanisms directly related to neuronal activity e. Although astrocytes do not generate action potentials per se they can actively modulate synaptic transmission and neuronal synchronization in mediating notably the release of vesicles-containing neurotransmitters and neuromodulators, such as glutamate, ATP, adenosine, and D-serine.
In the extracellular space ATP can be converted to adenosine by the dephosphorylating action of the ectonucleotidase anchored at the plasma membrane Joseph et al. D-serine that can be released from astrocytes was also shown to modulate electrical neurotransmission by acting at the glycine binding site of NMDA receptor Stevens et al.
Interestingly, the number of astrocytic processes, as well as their contact with active synapses, are stimulated by extracellular glutamate and also involve actin-dependent mechanisms Cornell-Bell et al. Yet, the cooperative action of astrocytes in culture was shown to protect neurons against ROS toxicity Desagher et al.
The thiol group of the glutathione molecule acts as an important electron donor. While both neurons and astrocytes synthesize glutathione, neuronal glutathione levels are higher in the presence of astrocytes Dringen et al.
Glutathione transport across cells is notably mediated by multidrug resistance proteins MRP that belong to the subgroup ABCC of the ATP-binding cassette transporters, which mediate passage via ATP hydrolysis Borst and Elferink, ; Dringen and Hirrlinger, ; Figure 5. Activation of astrocytic glutamate receptors was shown to translocate nuclear factor-erythroid 2-realted factor-2 Nrf2 present in lower concentrations in neurons into the nucleus and to trigger the expression of antioxidant genes, notably related to glutathione metabolism Jimenez-Blasco et al.
Astrocytes synthesize large amount of hydrogen sulfide, which was demonstrated to not only have neuroprotective properties Lee et al. Ascorbate is also another important antioxidant anion in the brain and glutamate was demonstrated to stimulate its release from astrocytes Wilson et al.
Astrocytes are responsible for the recycling of the neuronal extracellularly released dehydroascorbic acid the oxidized form of ascorbate into ascorbate, which can be exported to neurons Covarrubias-Pinto et al. Extracellular transport of ascorbate from astrocytes is believed to be mediated by volume-sensitive organic osmolyte-anion channel VSOAC that requires non-hydrolytic ATP binding Jackson et al.
Considering the fact that efficacy of the mechanisms stimulated by astrocytic glutamate uptake depends on the density of the transporters at the plasma membrane Robinson, , efficient trafficking of EAAT2-containing vesicles and exocytosis must moreover take place Stenovec et al.
Glycogenesis glycogen production from glucose 1-phosphate by glycogen synthase and glycogenolysis glycogen breakdown to glucose 6-phosphate by the combined action of glycogen phosphorylase and phosphoglucomutase mainly occurs in astrocytes Dringen et al. In line with this, glycogen levels were found to increase with anesthesia Morgenthaler et al.
However, no change in brain glycogen level was measured during visual stimulation in humans Oz et al. While glycogen-derived lactate has been demonstrated to have a pivotal role in memory formation and consolidation Gibbs and Hertz, ; Suzuki et al.
Recently, astrocytic glycogenolysis was shown to provide energy to sustain glutamatergic neurotransmission i. Glycogen might act as a substrate for de novo formation of glutamate Gibbs et al. While the essential role of astrocytes to cerebral function is now widely accepted, quantitative assessment of their actual contribution to energy metabolism has been missing, notably because the methodologies did not allow differentiating between neurons and astrocytes.
Direct 13 C MRS along with advanced metabolic modeling can provide measurements of both neuronal and glial metabolism in specific brain regions and under various activation states.
In this context, new data indicate that the rate of astrocytic metabolism is about half of that in neurons, and can be activated by sensory stimulation and that the astrocytic response amplitude can be, in absolute terms, as large as in neurons, suggesting that the changes in ATP requirements associated with the glutamate-glutamine cycle are coupled with the ATP produced by glucose oxidation in both compartments.
Increase in neuronal metabolism likely supports neurotransmission-associated functions, such as restoration of ion gradients caused by action potentials, post-synaptic currents, and transport of glutamate into vesicles.
Adaptation of glial metabolism also provides energy for neurotransmission besides housekeeping tasks, likely fueling the production and action of modulators of neuronal activity and of synaptic plasticity, supply of antioxidant molecules and neurotrophic factors that are necessary for adequate brain function, and regulation of blood flow and volume.
Astrocytes are moreover important source of glycogen that can be used specifically for neurotransmission support. Progress in MR detection methods of 1 H and non- 1 H nuclei is a promising direction for more detailed and complete metabolic dataset acquisition.
While this provides insights into cellular function in vivo , it also requires improvement of current metabolic models describing best energy metabolism. Simultaneous acquisition of other types of data, such as electrical activity and blood flow, might contribute to more precise characterization of the coupling between brain function and energy metabolism by MRS.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The authors' research is supported by the Swiss National Science Foundation to JD and to RG ; the National Competence Center in Biomedical Imaging NCCBI ; and by Centre d'Imagerie BioMédicale CIBM of the UNIL, UNIGE, HUG, CHUV, EPFL, and the Leenaards and Jeantet Foundations. Abe, K. The possible role of hydrogen sulfide as an endogenous neuromodulator.
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This study was supported by the Program for Neuropsychiatric Research, McLean Hospital BMC and NRF grants R1A2B, R1H1A, IITP grant from MSIT HS.
The authors want to thank Ryan A. Healy, Yoon Lee, Wang Liao, Miseon Oh, and Jinfeng Xuan for technical, and Suzanne Babb, Fontini Savvides, and Tamare V. Adrien for administrative help.
The authors also thank Dr. Rosario Sanchez-Pernaute and Dr. Christian LeGuern for critically reading the manuscript and helpful discussions. Department of Psychiatry, Harvard Medical School, Belmont, MA, USA. Woo-In Ryu, Mariana K. Bormann, Minqi Shen, Brent Forester, Kai-C. Basic Neuroscience Division, Harvard Medical School, Belmont, MA, USA.
Program for Neuropsychiatric Research, McLean Hospital, Harvard Medical School, Belmont, MA, USA. Bormann, Minqi Shen, Kai-C. Department of Immunology, Tufts University School of Medicine, Boston, MA, USA. Mood Disorders Division and Geriatric Psychiatry Research Program, McLean Hospital, Harvard Medical School, Belmont, MA, USA.
Department of Molecular and Life Sciences, Center for Bionano Intelligence Education and Research, Hanyang University, Ansan, South Korea.
Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA. You can also search for this author in PubMed Google Scholar. All authors reviewed the manuscript. KCS and BMC conceptualized and designed, and BMC funded the study. WIR, MKB, MS, DK, YP, and JS performed the experiments.
KCS, WIR, MKB, and HS analyzed and interpreted the data, and KCS wrote the paper. BF recruited and diagnosed subjects. Correspondence to Kai-C. Sonntag or Bruce M. Open Access This article is licensed under a Creative Commons Attribution 4. Reprints and permissions. Ryu, WI. et al.
Mol Psychiatry 26 , — Download citation. Received : 20 August Revised : 01 March Accepted : 18 March Published : 16 April Issue Date : October Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article.
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Subjects Biochemistry Cell biology Diseases Neuroscience Stem cells. Full size image. Discussion LOAD is a complexly determined disorder characterized by a combination of multiple interacting pathological processes, some of which are genetically determined and inherent in neurodevelopment and in youth and some of which are part of the normal aging process.
Methods Subject population and cell derivation Subjects Supplementary Table 1 were recruited at the McLean Hospital Memory Diagnostic Clinic. Cell culture Cells were differentiated and propagated in standard tissue culture. Biochemical assays Bioenergetic parameters were determined using Seahorse XFp Cell Mito Stress Tests Seahorse, Agilent Technologies, Santa Clara, CA and the processing of bioenergetic substrates were assessed in Biolog MitoPlate S-1 assays Biolog, Hayward, CA.
Molecular assays Total RNA was isolated and purified using TRI-Reagent MilliporeSigma and RNA integrity was measured with an Agilent Bioanalyzer Agilent. Detailed information of the materials and methods is presented in the Supplement Information.
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The authors want to thank Ryan A. Healy, Yoon Lee, Wang Liao, Miseon Oh, and Jinfeng Xuan for technical, and Suzanne Babb, Fontini Savvides, and Tamare V. Adrien for administrative help. The authors also thank Dr. Rosario Sanchez-Pernaute and Dr.
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JCI Insight. Download references. The authors would like to thank Metabolon Inc. Durham, USA for the generation of metabolomics data and ChromaDex Inc.
Irvine, CA, USA for providing nicotinamide riboside. AM and HY acknowledge support from the PoLiMeR Innovative Training Network Marie Sklodowska-Curie Grant Agreement No. The computations were performed on resources provided by SNIC through Uppsala Multidisciplinary Center for Advanced Computational Science UPPMAX under Project sllstore Open access funding provided by Royal Institute of Technology.
This work was financially supported by ScandiBio Therapeutics and Knut and Alice Wallenberg Foundation Department of Neurology and Neuroscience, Faculty of Medicine, Alanya Alaaddin Keykubat University, Antalya, Turkey.
Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden. Department of Neurology, Faculty of Medicine, Istanbul Medipol University, Istanbul, Turkey.
Functional Imaging and Cognitive-Affective Neuroscience Lab, Istanbul Medipol University, Istanbul, Turkey. Department of Medical Pharmacology, Faculty of Medicine, Atatürk University, Erzurum, Turkey. Department of Pathology, Veterinary Faculty, Ataturk University, Erzurum, Turkey.
Department of Molecular Biology and Genetics, Faculty of Science, Erzurum Technical University, Erzurum, Turkey. Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden. Department of Medical Biology, Faculty of Medicine, Atatürk University, Erzurum, Turkey.
Department of Molecular and Clinical Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden. You can also search for this author in PubMed Google Scholar. Research project: conception: A. and B. and A. Y, and review and critique: A.
and M. All authors read and approved the final manuscript. Correspondence to Mathias Uhlén or Adil Mardinoglu. The ethics committee approved the study of Istanbul Medipol University, Istanbul, Turkey Date Written informed consent for publication was obtained from all participants before initiating any trial-related procedures.
AM, JB and MU are the founder and shareholders of ScandiBio Therapeutics. The other authors declare no competing interests. Collection of samples of CMA and placebo groups and the measured values of clinical indicators before and after treatment. Consort flow diagram. Diagram shows the progress through the phases of the parallel randomisation of drug and placebo groups.
Plasma metabolomics data for each patient before and after treatment and statistical analysis of plasma metabolites between different visits or groups.
The association between the plasma level of the four supplements serine, carnitine, cysteine and nicotinamide riboside with the plasma levels of other metabolites. Plasma proteomics data were generated with the Olink cardiometabolic, inflammation, neurology and oncology panels for each patient before and after treatment and statistical analysis of plasma proteins between different visits or groups.
Multi-Omics Network Data, including edges and nodes information. Open Access This article is licensed under a Creative Commons Attribution 4.
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Reprints and permissions. Yulug, B. et al. Transl Neurodegener 12 , 4 Download citation. Received : 24 October Accepted : 09 January Published : 26 January Anyone you share the following link with will be able to read this content:.
Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search all BMC articles Search. Download PDF. Methods Here, we designed a randomised, double-blinded, placebo-controlled phase-II clinical trial and studied the effect of CMA administration on the global metabolism of AD patients.
Conclusion Our results indicate that treatment of AD patients with CMA can lead to enhanced cognitive functions and improved clinical parameters associated with phenomics, metabolomics, proteomics and imaging analysis.
Materials and methods Clinical trial design and oversight Patients for this randomised, parallel-group, two-arm, double-blinded, placebo-controlled, phase 2 study were recruited at the Faculty of Medicine, Alanya Alaaddin Keykubat University, Antalya, Turkey and Faculty of Medicine, Istanbul Medipol University, Istanbul, Turkey.
Randomisation, interventions, and follow-up Patients were randomly assigned to receive CMA or placebo Outcomes The primary endpoint in the original protocol was to assess the clinical efficacy of CMA in AD patients. Proteomics analysis Plasma levels of proteins were determined with the Olink panels Olink Bioscience, Uppsala, Sweden.
Untargeted metabolomics analysis Plasma samples were collected on days 0 and 84 for untargeted metabolite profiling by Metabolon Durham, NC. Determination of clinical variables informing response to CMA administration The patient groups with low and high levels of each clinical parameter were established based on the median score for that clinical parameter across all patients on day 0.
Magnetic resonance imaging MRI parameters and analysis Among the entire patient cohort, 40 MRI-compatible patients, 29 in the CMA group and 11 in the placebo group, were recruited for the structural MRI study.
Image processing To obtain hippocampal subfield measurements, each T1 image was processed using FreeSurfer version 7. Statistical analysis Paired t -test was used to identify the differences in clinical parameters between time points, and one-way ANOVA was used to find the shifts between CMA and placebo groups at each time point.
Generation of multi-omics network A multi-omics correlation network was generated based on all patients' clinical parameters, serum chemistry, metabolomics, and proteomics data, following the multi-omics network generation pipeline from iNetModels [ 49 ]. RESULTS CMA improves cognition and clinical parameters in AD patients To test the effect of CMA in AD patients, we performed a double-blinded, randomised, placebo-controlled phase 2 study and screened 89 adults diagnosed with AD.
Full size image. Table 2 List of adverse effects Full size table. Table 3 Differences in ADAS-Cog, ADCS-ADL and MMSE scores in the CMA and placebo groups Full size table. Discussion Our results suggested that oral administration of CMA for 84 days has a considerable effect on cognitive function in AD patients based on ADAS-Cog scores.
Conclusions The present phase 2 clinical study suggested that oral administration of CMA improves metabolic alterations in AD patients, and that CMA is safe and well-tolerated, with no major safety concerns identified.
Availability of data and materials The data supporting the findings of this study are available in Supplementary Material. References Trujillo-Estrada L, Jimenez S, De Castro V, Torres M, Baglietto-Vargas D, Moreno-Gonzalez I, et al.
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Article Google Scholar Zhang C, Bjornson E, Arif M, Tebani A, Lovric A, Benfeitas R, et al. These findings indicate that lower energy generation rates might disrupt the long distance and large-scale neuronal communications—thereby leading to brain disorders.
Our study revealed the general principle of brain energy-activity organization and suggests that the metabolism-neural synchrony pathway could be a new potential treatment target for psychotic disorders. The highlighted cortical regions above are the nodes of a large-scale brain network.
These areas usually show synchronized neural activity or in other words, functional connectivity FC , as they work towards a common goal. In this study, a positive correlation was found between the strength of this synchronization or connectivity and the rate of the creatine kinase reaction, which would be critical for orchestrating oscillatory states, and enhancing the fidelity of information processing for better executive and cognitive function.
Xiaopeng Song is a postdoctoral fellow in the lab of Dr. Fei Du at McLean Hospital, Harvard Medical School. Learn more in the original research article: Bioenergetics and abnormal functional connectivity in psychotic disorders. Song X, Chen X, Yuksel C, Yuan J, Pizzagalli DA, Forester B, Öngür D, Du F.
Worldwide, Almond industry 55 million people had prevalent Thermogenic metabolism support inwhich is expected cogitive triple by Almond industry, especially in low- and middle-income countries ccognitive 1]. Lacking timely diagnosis and limited effective treatment for dementia make identifying risk factors Caloric needs for healthy aging cohnitive its early prevention, among which dietary factors have received increasing attention [ ccognitive. Recently, accumulating evidence from population-based Eergy has linked the temporal patterns of energy intake TPEIusually defined as the temporal distribution of energy intake during a day, to mortality and metabolic diseases [ 2], such as diabetes and hypertension. In vitro and in vivo studies also revealed that meal timing could drive metabolic alterations and circadian regulation [ 3], and disrupted meal timing altered the peripheral circadian clocks in the hippocampus and consequently affected cognitive function [ 4]. However, population-level evidence on the association between the TPEI and cognitive function remains lacking. We thus aimed to examine this relationship in the China Health and Nutrition Survey from toa community-based cohort study with national representativeness [ 5]. Oxford University Press is a department of the University of Oxford.
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