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...

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Autores principales:	Tim Ebert, Daniel E. Heinz, Suellen Almeida-Corrêa, Renata Cruz, Frederik Dethloff, Tibor Stark, Thomas Bajaj, Oriana M. Maurel, Fabiola M. Ribeiro, Silvio Calcagnini, Kathrin Hafner, Nils C. Gassen, Christoph W. Turck, Benoit Boulat, Michael Czisch, Carsten T. Wotjak
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	spatial memory biomarker MRS MCI glia astrocytes Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/1c3f47f1e2ad4e5ab5d21e8c3ed79cbb
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spelling	oai:doaj.org-article:1c3f47f1e2ad4e5ab5d21e8c3ed79cbb2021-11-12T06:00:26ZMyo-Inositol Levels in the Dorsal Hippocampus Serve as Glial Prognostic Marker of Mild Cognitive Impairment in Mice1663-436510.3389/fnagi.2021.731603https://doaj.org/article/1c3f47f1e2ad4e5ab5d21e8c3ed79cbb2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnagi.2021.731603/fullhttps://doaj.org/toc/1663-4365Dementia 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.Tim EbertTim EbertDaniel E. HeinzDaniel E. HeinzSuellen Almeida-CorrêaRenata CruzFrederik DethloffTibor StarkTibor StarkTibor StarkThomas BajajOriana M. MaurelFabiola M. RibeiroSilvio CalcagniniKathrin HafnerNils C. GassenNils C. GassenChristoph W. TurckBenoit BoulatMichael CzischCarsten T. WotjakCarsten T. WotjakFrontiers Media S.A.articlespatial memorybiomarkerMRSMCIgliaastrocytesNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Aging Neuroscience, Vol 13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	spatial memory biomarker MRS MCI glia astrocytes Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	spatial memory biomarker MRS MCI glia astrocytes Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 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
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.
format	article
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
title	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_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_sort	myo-inositol levels in the dorsal hippocampus serve as glial prognostic marker of mild cognitive impairment in mice
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/1c3f47f1e2ad4e5ab5d21e8c3ed79cbb
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Myo-Inositol Levels in the Dorsal Hippocampus Serve as Glial Prognostic Marker of Mild Cognitive Impairment in Mice

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