Myo-Inositol Levels in the Dorsal Hippocampus Serve as Glial Prognostic Marker of Mild Cognitive Impairment in Mice
Dementia is a devastating age-related disorder. Its therapy would largely benefit from the identification of susceptible subjects at early, prodromal stages of the disease. To search for such prognostic markers of cognitive impairment, we studied spatial navigation in male BALBc vs. B6N mice in comb...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2021.731603/full |
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| author | Tim Ebert Tim Ebert Daniel E. Heinz Daniel E. Heinz Suellen Almeida-Corrêa Renata Cruz Frederik Dethloff Tibor Stark Tibor Stark Tibor Stark Thomas Bajaj Oriana M. Maurel Fabiola M. Ribeiro Silvio Calcagnini Kathrin Hafner Nils C. Gassen Nils C. Gassen Christoph W. Turck Benoit Boulat Michael Czisch Carsten T. Wotjak Carsten T. Wotjak |
| author_facet | Tim Ebert Tim Ebert Daniel E. Heinz Daniel E. Heinz Suellen Almeida-Corrêa Renata Cruz Frederik Dethloff Tibor Stark Tibor Stark Tibor Stark Thomas Bajaj Oriana M. Maurel Fabiola M. Ribeiro Silvio Calcagnini Kathrin Hafner Nils C. Gassen Nils C. Gassen Christoph W. Turck Benoit Boulat Michael Czisch Carsten T. Wotjak Carsten T. Wotjak |
| author_sort | Tim Ebert |
| collection | DOAJ |
| description | Dementia is a devastating age-related disorder. Its therapy would largely benefit from the identification of susceptible subjects at early, prodromal stages of the disease. To search for such prognostic markers of cognitive impairment, we studied spatial navigation in male BALBc vs. B6N mice in combination with in vivo magnetic resonance spectroscopy (1H-MRS). BALBc mice consistently showed higher escape latencies than B6N mice, both in the Water Cross Maze (WCM) and the Morris water maze (MWM). These performance deficits coincided with higher levels of myo-inositol (mIns) in the dorsal hippocampus before and after training. Subsequent biochemical analyses of hippocampal specimens by capillary immunodetection and liquid chromatography mass spectrometry-based (LC/MS) metabolomics revealed a higher abundance of glial markers (IBA-1, S100B, and GFAP) as well as distinct alterations in metabolites including a decrease in vitamins (pantothenic acid and nicotinamide), neurotransmitters (acetylcholine), their metabolites (glutamine), and acetyl-L-carnitine. Supplementation of low abundant acetyl-L-carnitine via the drinking water, however, failed to revert the behavioral deficits shown by BALBc mice. Based on our data we suggest (i) BALBc mice as an animal model and (ii) hippocampal mIns levels as a prognostic marker of mild cognitive impairment (MCI), due to (iii) local changes in microglia and astrocyte activity, which may (iv) result in decreased concentrations of promnesic molecules. |
| first_indexed | 2024-12-23T19:20:36Z |
| format | Article |
| id | doaj.art-1c3f47f1e2ad4e5ab5d21e8c3ed79cbb |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-23T19:20:36Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-1c3f47f1e2ad4e5ab5d21e8c3ed79cbb2022-12-21T17:34:10ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652021-11-011310.3389/fnagi.2021.731603731603Myo-Inositol Levels in the Dorsal Hippocampus Serve as Glial Prognostic Marker of Mild Cognitive Impairment in MiceTim Ebert0Tim Ebert1Daniel E. Heinz2Daniel E. Heinz3Suellen Almeida-Corrêa4Renata Cruz5Frederik Dethloff6Tibor Stark7Tibor Stark8Tibor Stark9Thomas Bajaj10Oriana M. Maurel11Fabiola M. Ribeiro12Silvio Calcagnini13Kathrin Hafner14Nils C. Gassen15Nils C. Gassen16Christoph W. Turck17Benoit Boulat18Michael Czisch19Carsten T. Wotjak20Carsten T. Wotjak21Research Group Neuronal Plasticity, Max Planck Institute of Psychiatry, Munich, GermanyResearch Group Neurohomeostasis, Department of Psychiatry and Psychotherapy, University Hospital Bonn, Bonn, GermanyResearch Group Neuronal Plasticity, Max Planck Institute of Psychiatry, Munich, GermanyMax Planck School of Cognition, Leipzig, GermanyResearch Group Neuronal Plasticity, Max Planck Institute of Psychiatry, Munich, GermanyResearch Group Neuronal Plasticity, Max Planck Institute of Psychiatry, Munich, GermanyProteomics and Biomarkers, Max Planck Institute of Psychiatry, Munich, GermanyResearch Group Neuronal Plasticity, Max Planck Institute of Psychiatry, Munich, GermanyDepartment of Pharmacology, Faculty of Medicine, Masaryk University, Brno, CzechiaScientific Core Unit “Neuroimaging”, Max Planck Institute of Psychiatry, Munich, GermanyResearch Group Neurohomeostasis, Department of Psychiatry and Psychotherapy, University Hospital Bonn, Bonn, GermanyResearch Group Neuronal Plasticity, Max Planck Institute of Psychiatry, Munich, GermanyResearch Group Neuronal Plasticity, Max Planck Institute of Psychiatry, Munich, GermanyResearch Group Neuronal Plasticity, Max Planck Institute of Psychiatry, Munich, GermanyDepartment of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, GermanyResearch Group Neurohomeostasis, Department of Psychiatry and Psychotherapy, University Hospital Bonn, Bonn, GermanyDepartment of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, GermanyProteomics and Biomarkers, Max Planck Institute of Psychiatry, Munich, GermanyScientific Core Unit “Neuroimaging”, Max Planck Institute of Psychiatry, Munich, GermanyScientific Core Unit “Neuroimaging”, Max Planck Institute of Psychiatry, Munich, GermanyResearch Group Neuronal Plasticity, Max Planck Institute of Psychiatry, Munich, GermanyCentral Nervous System Diseases Research (CNSDR), Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, GermanyDementia is a devastating age-related disorder. Its therapy would largely benefit from the identification of susceptible subjects at early, prodromal stages of the disease. To search for such prognostic markers of cognitive impairment, we studied spatial navigation in male BALBc vs. B6N mice in combination with in vivo magnetic resonance spectroscopy (1H-MRS). BALBc mice consistently showed higher escape latencies than B6N mice, both in the Water Cross Maze (WCM) and the Morris water maze (MWM). These performance deficits coincided with higher levels of myo-inositol (mIns) in the dorsal hippocampus before and after training. Subsequent biochemical analyses of hippocampal specimens by capillary immunodetection and liquid chromatography mass spectrometry-based (LC/MS) metabolomics revealed a higher abundance of glial markers (IBA-1, S100B, and GFAP) as well as distinct alterations in metabolites including a decrease in vitamins (pantothenic acid and nicotinamide), neurotransmitters (acetylcholine), their metabolites (glutamine), and acetyl-L-carnitine. Supplementation of low abundant acetyl-L-carnitine via the drinking water, however, failed to revert the behavioral deficits shown by BALBc mice. Based on our data we suggest (i) BALBc mice as an animal model and (ii) hippocampal mIns levels as a prognostic marker of mild cognitive impairment (MCI), due to (iii) local changes in microglia and astrocyte activity, which may (iv) result in decreased concentrations of promnesic molecules.https://www.frontiersin.org/articles/10.3389/fnagi.2021.731603/fullspatial memorybiomarkerMRSMCIgliaastrocytes |
| spellingShingle | Tim Ebert Tim Ebert Daniel E. Heinz Daniel E. Heinz Suellen Almeida-Corrêa Renata Cruz Frederik Dethloff Tibor Stark Tibor Stark Tibor Stark Thomas Bajaj Oriana M. Maurel Fabiola M. Ribeiro Silvio Calcagnini Kathrin Hafner Nils C. Gassen Nils C. Gassen Christoph W. Turck Benoit Boulat Michael Czisch Carsten T. Wotjak Carsten T. Wotjak Myo-Inositol Levels in the Dorsal Hippocampus Serve as Glial Prognostic Marker of Mild Cognitive Impairment in Mice Frontiers in Aging Neuroscience spatial memory biomarker MRS MCI glia astrocytes |
| title | Myo-Inositol Levels in the Dorsal Hippocampus Serve as Glial Prognostic Marker of Mild Cognitive Impairment in Mice |
| title_full | Myo-Inositol Levels in the Dorsal Hippocampus Serve as Glial Prognostic Marker of Mild Cognitive Impairment in Mice |
| title_fullStr | Myo-Inositol Levels in the Dorsal Hippocampus Serve as Glial Prognostic Marker of Mild Cognitive Impairment in Mice |
| title_full_unstemmed | Myo-Inositol Levels in the Dorsal Hippocampus Serve as Glial Prognostic Marker of Mild Cognitive Impairment in Mice |
| title_short | Myo-Inositol Levels in the Dorsal Hippocampus Serve as Glial Prognostic Marker of Mild Cognitive Impairment in Mice |
| title_sort | myo inositol levels in the dorsal hippocampus serve as glial prognostic marker of mild cognitive impairment in mice |
| topic | spatial memory biomarker MRS MCI glia astrocytes |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2021.731603/full |
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