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Journal Article

Myo-Inositol Levels in the Dorsal Hippocampus Serve as Glial Prognostic Marker of Mild Cognitive Impairment in Mice

MPS-Authors
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Ebert,  Tim
RG Neuronal Plasticity, Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

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Heinz,  Daniel E.
RG Neuronal Plasticity, Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

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Almeida-Correa,  Suellen
RG Neuronal Plasticity, Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

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Cruz,  Renata
RG Neuronal Plasticity, Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

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Dethloff,  Frederik
RG Proteomics and Biomarkers, Max Planck Institute of Psychiatry, Max Planck Society;

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Stark,  Tibor
RG Neuronal Plasticity, Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

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Maurel,  Oriana M.
RG Neuronal Plasticity, Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

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Ribeiro,  Fabiola M.
RG Neuronal Plasticity, Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

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Calcagnini,  Silvio
RG Neuronal Plasticity, Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

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Hafner,  Kathrin
Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

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Gassen,  Nils C.
Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

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Turck,  Christoph W.
RG Proteomics and Biomarkers, Max Planck Institute of Psychiatry, Max Planck Society;

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Boulat,  Benoit
Max Planck Institute of Psychiatry, Max Planck Society;

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Czisch,  Michael
Max Planck Institute of Psychiatry, Max Planck Society;

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Wotjak,  Carsten T.
RG Neuronal Plasticity, Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

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Citation

Ebert, T., Heinz, D. E., Almeida-Correa, S., Cruz, R., Dethloff, F., Stark, T., et al. (2021). Myo-Inositol Levels in the Dorsal Hippocampus Serve as Glial Prognostic Marker of Mild Cognitive Impairment in Mice. FRONTIERS IN AGING NEUROSCIENCE, 13: 731603. doi:10.3389/fnagi.2021.731603.


Cite as: https://hdl.handle.net/21.11116/0000-0009-C874-3
Abstract
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 (H-1-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.