A single dose of glycogen phosphorylase inhibitor improves cognitive functions of aged mice and affects the concentrations of metabolites in the brain.
Behavioral tests
Brain aging
Glycogen phosphorylase (pyg)
Hippocampus
Memory formation
Metabolomics
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
15 10 2024
15 10 2024
Historique:
received:
24
05
2024
accepted:
30
09
2024
medline:
16
10
2024
pubmed:
16
10
2024
entrez:
15
10
2024
Statut:
epublish
Résumé
Inhibition of glycogen phosphorylase (Pyg) - a regulatory enzyme of glycogen phosphorolysis - influences memory formation in rodents. We have previously shown that 2-week intraperitoneal administration of a Pyg inhibitor BAY U6751 stimulated the "rejuvenation" of the hippocampal proteome and dendritic spines morphology and improved cognitive skills of old mice. Given the tedious nature of daily intraperitoneal drug administration, in this study we investigated whether a single dose of BAY U6751 could induce enduring behavioral effects. Obtained results support the efficacy of such treatment in significantly improving the cognitive performance of 20-22-month-old mice. Metabolomic analysis of alterations observed in the hippocampus, cerebellum, and cortex reveal that the inhibition of glycogen phosphorolysis impacts not only glucose metabolism but also various other metabolic processes.
Identifiants
pubmed: 39406810
doi: 10.1038/s41598-024-74861-z
pii: 10.1038/s41598-024-74861-z
doi:
Substances chimiques
Glycogen Phosphorylase
EC 2.4.1.-
Enzyme Inhibitors
0
1,4-dideoxy-1,4-iminoarabinitol
100937-53-9
Imino Furanoses
0
Arabinose
B40ROO395Z
Sugar Alcohols
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
24123Subventions
Organisme : Polish National Science Centre
ID : UMO-2020/37/B/NZ4/00808.
Informations de copyright
© 2024. The Author(s).
Références
Gibbs, M. E., O’dowd, B. S., Hertz, E. & Hertz, L. Astrocytic energy metabolism consolidates memory in young chicks. Neuroscience. 141, 9–13 (2006).
pubmed: 16750889
doi: 10.1016/j.neuroscience.2006.04.038
Drulis-Fajdasz, D. et al. Glycogen phosphorylase inhibition improves cognitive function of aged mice. Aging Cell.22, 1–18. https://doi.org/10.1111/acel.13928 (2023).
Suzuki, A. et al. Astrocyte-neuron lactate transport is required for long-term memory formation. Cell. 144, 810–823 (2011).
pubmed: 21376239
pmcid: 3073831
doi: 10.1016/j.cell.2011.02.018
Drulis-Fajdasz, D. et al. Involvement of cellular metabolism in age-related LTP modifications in rat hippocampal slices. Oncotarget. 6, 14065–14081 (2015).
pubmed: 26101857
pmcid: 4546452
doi: 10.18632/oncotarget.4188
Magistretti, P. J. & Allaman, I. A Cellular Perspective on Brain Energy Metabolism and Functional Imaging. Neuron. 86, 883–901 (2015).
pubmed: 25996133
doi: 10.1016/j.neuron.2015.03.035
Drulis-Fajdasz, D., Gizak, A., Wójtowicz, T., Wiśniewski, J. R. & Rakus, D. Aging-associated changes in hippocampal glycogen metabolism in mice. Evidence for and against astrocyte-to-neuron lactate shuttle. Glia. 66, 1481–1495 (2018).
pubmed: 29493012
pmcid: 6001795
doi: 10.1002/glia.23319
Drulis-Fajdasz, D., Gostomska-Pampuch, K., Duda, P., Wiśniewski, J. R. & Rakus, D. Quantitative proteomics reveals significant differences between mouse brain formations in expression of proteins involved in neuronal plasticity during aging. Cells. 10, 1-26 (2021).
Zhu, X. H., Lu, M., Lee, B. Y., Ugurbil, K. & Chen, W. In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences. Proc. Natl. Acad. Sci. U S A. 112, 2876–2881 (2015).
pubmed: 25730862
pmcid: 4352772
doi: 10.1073/pnas.1417921112
Fang, W. et al. Metabolomics in aging research: aging markers from organs. Front. Cell. Dev. Biol.11, 1–21 (2023).
doi: 10.3389/fcell.2023.1198794
Ryan, D., Robards, K. & Metabolomics The greatest omics of them all? Anal. Chem.78, 7954–7958 (2006).
pubmed: 17134127
doi: 10.1021/ac0614341
Ivanisevic, J. et al. Metabolic drift in the aging brain. Aging (Albany NY). 8, 1000–1020 (2016).
pubmed: 27182841
doi: 10.18632/aging.100961
Abreu, A. C., Navas, M. M., Fernandez, C. P., Sanchez-Santed, F. & Fernandez, I. NMR-Based Metabolomics Approach to explore Brain Metabolic Changes Induced by prenatal exposure to Autism-Inducing Chemicals. ACS Chem. Biol.16, 753–765 (2021).
pubmed: 33728896
doi: 10.1021/acschembio.1c00053
Gonzalez-Riano, C., Garcia, A. & Barbas, C. Metabolomics studies in brain tissue: a review. J. Pharm. Biomed. Anal.130, 141–168 (2016).
pubmed: 27451335
doi: 10.1016/j.jpba.2016.07.008
Akimoto, H. et al. Changes in brain metabolites related to stress resilience: metabolomic analysis of the hippocampus in a rat model of depression. Behav. Brain Res.359, 342–352 (2019).
pubmed: 30447240
doi: 10.1016/j.bbr.2018.11.017
Zheng, H. et al. Analysis of neuron-astrocyte metabolic cooperation in the brain of db/db mice with cognitive decline using 13 C NMR spectroscopy. J. Cereb. Blood Flow. Metab.37, 332–343 (2017).
pubmed: 26762505
doi: 10.1177/0271678X15626154
Crook, A. A. & Powers, R. Quantitative NMR-Based Biomedical Metabolomics: current status and applications. Molecules. 25, 1-33 (2020).
Beckonert, O. et al. Metabolic profiling, metabolomic and metabonomic procedures for NMR spectroscopy of urine, plasma, serum and tissue extracts. Nat. Protoc.2, 2692–2703 (2007).
pubmed: 18007604
doi: 10.1038/nprot.2007.376
Warburton, E. C. & Brown, M. W. Findings from animals concerning when interactions between perirhinal cortex, hippocampus and medial prefrontal cortex are necessary for recognition memory. Neuropsychologia. 48, 2262–2272 (2010).
pubmed: 20026141
doi: 10.1016/j.neuropsychologia.2009.12.022
Bannerman, D. M. et al. Hippocampal synaptic plasticity, spatial memory and anxiety. Nat. Rev. Neurosci.15, 181–192 (2014).
pubmed: 24552786
doi: 10.1038/nrn3677
Harris, M. A., Wiener, J. M. & Wolbers, T. Aging specifically impairs switching to an allocentric navigational strategy. Front. Aging Neurosci.4, 1–9 (2012).
doi: 10.3389/fnagi.2012.00029
Grayson, B. et al. Assessment of disease-related cognitive impairments using the novel object recognition (NOR) task in rodents. Behav. Brain Res.285, 176–193 (2015).
pubmed: 25447293
doi: 10.1016/j.bbr.2014.10.025
Antunes, M. & Biala, G. The novel object recognition memory: Neurobiology, test procedure, and its modifications. Cogn. Process.13, 93–110 (2012).
pubmed: 22160349
doi: 10.1007/s10339-011-0430-z
Denninger, J. K., Smith, B. M. & Kirby, E. D. Novel object recognition and object location behavioral testing in mice on a budget. J. Vis. Exp.20, 1–10 (2018).
Chhetri, D. R. Myo-Inositol and its derivatives: their emerging role in the treatment of human diseases. Front. Pharmacol.10, 1–8 (2019).
doi: 10.3389/fphar.2019.01172
Castro, M. A., Beltrán, F. A., Brauchi, S. & Concha I. I. A metabolic switch in brain: glucose and lactate metabolism modulation by ascorbic acid. J. Neurochem. 110, 423–440 (2009).
pubmed: 19457103
doi: 10.1111/j.1471-4159.2009.06151.x
Waniewski, R. A. & Martin, D. L. Preferential utilization of acetate by astrocytes is attributable to transport. J. Neurosci.18, 5225–5233 (1998).
pubmed: 9651205
pmcid: 6793490
doi: 10.1523/JNEUROSCI.18-14-05225.1998
Manto, M. et al. Consensus paper: roles of the cerebellum in motor control-the diversity of ideas on cerebellar involvement in movement. Cerebellum. 11, 457–487 (2012).
pubmed: 22161499
pmcid: 4347949
doi: 10.1007/s12311-011-0331-9
Bird, C. M. & Burgess, N. The hippocampus and memory: insights from spatial processing. Nat. Rev. Neurosci.9, 182–194 (2008).
pubmed: 18270514
doi: 10.1038/nrn2335
Rozycka, A. et al. Glutamate, GABA, and presynaptic markers involved in neurotransmission are differently affected by age in distinct mouse brain regions. ACS Chem. Neurosci.10, 4449–4461 (2019).
pubmed: 31556991
doi: 10.1021/acschemneuro.9b00220
Rozycka, A. & Liguz-Lecznar, M. The space where aging acts: focus on the GABAergic synapse. Aging Cell.16, 634–643 (2017).
pubmed: 28497576
pmcid: 5506442
doi: 10.1111/acel.12605
Fontana, A. C. K. current approaches to enhance glutamate transporter function and expression. J. Neurochem. 134, 982–1007 (2015).
pubmed: 26096891
doi: 10.1111/jnc.13200
Waagepetersen, H. S., Sonnewald, U., Larsson, O. M. & Schousboe, A. A possible role of alanine for ammonia transfer between astrocytes and glutamatergic neurons. J. Neurochem. 75, 471–479 (2000).
pubmed: 10899921
doi: 10.1046/j.1471-4159.2000.0750471.x
Dadsetan, S. et al. Brain alanine formation as an ammonia-scavenging pathway during hyperammonemia: effects of glutamine synthetase inhibition in rats and astrocyte-neuron co-cultures. J. Cereb. Blood Flow. Metab.33, 1235–1241 (2013).
pubmed: 23673435
pmcid: 3734774
doi: 10.1038/jcbfm.2013.73
Schousboe, A., Sonnewald, U. & Waagepetersen, H. S. Differential roles of alanine in GABAergic and glutamatergic neurons. Neurochem Int.43, 311–315 (2003).
pubmed: 12742074
doi: 10.1016/S0197-0186(03)00017-2
Marcucci, H., Paoletti, L., Jackowski, S. & Banchio, C. Phosphatidylcholine biosynthesis during neuronal differentiation and its role in cell fate determination. J. Biol. Chem.285, 25382–25393 (2010).
pubmed: 20525991
pmcid: 2919101
doi: 10.1074/jbc.M110.139477
Magaquian, D., Delgado Ocaña, S., Perez, C. & Banchio, C. Phosphatidylcholine restores neuronal plasticity of neural stem cells under inflammatory stress. Sci. Rep.11, 1–12 (2021).
doi: 10.1038/s41598-021-02361-5
Ellison, D. W., Beal, M. F. & Martin, J. B. Phosphoethanolamine and ethanolamine are decreased in Alzheimer’s disease and Huntington’s disease. Brain Res.417, 389–392 (1987).
pubmed: 2958109
doi: 10.1016/0006-8993(87)90471-9
Klunk, W. E., Debnath, M. L., McClure, R. J. & Pettegrew, J. W. Inactivity of phosphoethanolamine, an endogenous GABA analog decreased in Alzheimer’s disease, at GABA binding sites. Life Sci.56, 2377–2383 (1995).
pubmed: 7791524
doi: 10.1016/0024-3205(95)00231-T
Blusztajn, J. K. & Slack, B. E. Accelerated breakdown of Phosphatidylcholine and Phosphatidylethanolamine is a predominant brain metabolic defect in Alzheimer’s Disease. J. Alzheimer’s Dis.93, 1285–1289 (2023).
doi: 10.3233/JAD-230061
Carter, A. J., Müller, R. E., Pschorn, U. & Stransky, W. Preincubation with Creatine Enhances Levels of Creatine Phosphate and prevents anoxic damage in rat hippocampal slices. J. Neurochem. 64, 2691–2699 (1995).
pubmed: 7760049
doi: 10.1046/j.1471-4159.1995.64062691.x
Jost, C. R. et al. Creatine kinase B-driven energy transfer in the brain is important for habituation and spatial learning behaviour, mossy fibre field size and determination of seizure susceptibility. Eur. J. Neurosci.15, 1692–1706 (2002).
pubmed: 12059977
doi: 10.1046/j.1460-9568.2002.02001.x
Majkutewicz, I. et al. Age-dependent effects of dimethyl fumarate on cognitive and neuropathological features in the streptozotocin-induced rat model of Alzheimer’s disease. Brain Res.1686, 19–33 (2018).
pubmed: 29453958
doi: 10.1016/j.brainres.2018.02.016
Popesco, M. C. et al. Serial analysis of gene expression profiles of adult and aged mouse cerebellum. Neurobiol. Aging. 29, 774–788 (2008).
pubmed: 17267076
doi: 10.1016/j.neurobiolaging.2006.12.006
Woodruff-Pak, D. et al. Differential effects and rates of normal aging in cerebellum and hippocampus. Proc. Natl. Acad. Sci. U. S. A.107, 1624–1629 (2010).
pubmed: 20080589
pmcid: 2824421
doi: 10.1073/pnas.0914207107
Kaiser, L. G., Schuff, N., Cashdollar, N. & Weiner, M. W. Age-related glutamate and glutamine concentration changes in normal human brain: 1H MR spectroscopy study at 4 T. Neurobiol. Aging. 26, 665–672 (2005).
pubmed: 15708441
pmcid: 2443746
doi: 10.1016/j.neurobiolaging.2004.07.001
Lu, Y. et al. Multi-omics analysis reveals neuroinflammation, activated glial signaling, and dysregulated synaptic signaling and metabolism in the hippocampus of aged mice. Front. Aging Neurosci.14, 1–18 (2022).
doi: 10.3389/fnagi.2022.964429
Gudi, V., Grieb, P., Linker, R. A. & Skripuletz, T. CDP-choline to promote remyelination in multiple sclerosis: the need for a clinical trial. Neural Regen Res.18, 2599–2605 (2023).
pubmed: 37449595
pmcid: 10358672
doi: 10.4103/1673-5374.373671
Magistretti, P. J. & Allaman, I. Lactate in the brain: from metabolic end-product to signalling molecule. Nat. Rev. Neurosci.19, 235–249 (2018).
pubmed: 29515192
doi: 10.1038/nrn.2018.19
Gizak, A., Duda, P., Wisniewski, J. & Rakus, D. Fructose-1,6-bisphosphatase: from a glucose metabolism enzyme to multifaceted regulator of a cell fate. Adv. Biol. Regul.72, 41–50 (2019).
pubmed: 30871972
doi: 10.1016/j.jbior.2019.03.001
Duda, P. et al. Fructose 1,6-Bisphosphatase 2 plays a crucial role in the induction and maintenance of long-term potentiation. Cells. 9, 1–22 (2020).
doi: 10.3390/cells9061375
Duran, J., Saez, I., Gruart, A., Guinovart, J. J. & Delgado-García, J. M. Impairment in long-term memory formation and learning-dependent synaptic plasticity in mice lacking glycogen synthase in the brain. J. Cereb. Blood Flow. Metab.33, 550–556 (2013).
pubmed: 23281428
pmcid: 3618391
doi: 10.1038/jcbfm.2012.200
Brown, A. M. Brain glycogen re-awakened. J. Neurochem. 89, 537–552 (2004).
pubmed: 15086511
doi: 10.1111/j.1471-4159.2004.02421.x
Bak, L. K. & Walls, A. B. Astrocytic glycogen metabolism in the healthy and diseased brain. J. Biol. Chem.293, 7108–7116 (2018).
pubmed: 29572349
pmcid: 5950001
doi: 10.1074/jbc.R117.803239
Haydon, P. G. & Glia Listening and talking to the synapse. Nat. Rev. Neurosci.2, 185–193 (2001).
pubmed: 11256079
doi: 10.1038/35058528
Yang, J. et al. Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons. Proc. Natl. Acad. Sci. U S A. 111, 12228–12233 (2014).
pubmed: 25071212
pmcid: 4143009
doi: 10.1073/pnas.1322912111
Wu, L., Butler, N. J. M. & Swanson, R. A. Technical and comparative aspects of brain glycogen metabolism. Adv. Neurobiol.23, 169–185 (2019).
pubmed: 31667809
doi: 10.1007/978-3-030-27480-1_6
Pudelko-Malik, N., Wiśniewski, J., Drulis-Fajdasz, D. & Mlynarz, P. Validated liquid chromatography-mass spectrometry method for the quantification of glycogenolysis phosphorylase inhibitor in mouse tissues – 5-isopropyl-4-(2-chlorophenyl)-1-ethyl-1,4-dihydro-6-methyl-2,3,5-pyridinetricarboxylic acid ester disodium salt hydrate. J. Sep. Sci.45, 3791–3799 (2022).
pubmed: 35964279
doi: 10.1002/jssc.202200454
Bergans, N., Stalmans, W., Goldmann, S. & Vanstapel, F. Molecular mode of inhibition of glycogenolysis in rat liver by the dihydropyridine derivative, BAY R3401: inhibition and inactivition of glycogen phosphorylase by an activated metabolite. Diabetes. 49, 1419–1426 (2000).
pubmed: 10969824
doi: 10.2337/diabetes.49.9.1419
Tomasi, G., Van Den Berg, F. & Andersson, C. Correlation optimized warping and dynamic time warping as preprocessing methods for chromatographic data. J. Chemom. 18, 231–241 (2004).
doi: 10.1002/cem.859
Savorani, F., Tomasi, G. & Engelsen, S. B. Icoshift: a versatile tool for the rapid alignment of 1D NMR spectra. J. Magn. Reson.202, 190–202 (2010).
pubmed: 20004603
doi: 10.1016/j.jmr.2009.11.012
Dieterle, F., Ross, A. & Senn, H. Probabilistic quotient normalization as robust method to aacount for dilution of complex biuological mixtures. Anal. chem.78, 4281–4290 (2006).
pubmed: 16808434
doi: 10.1021/ac051632c