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

J 2021

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

EBERT, Tim, Daniel E. HEINZ, Suellen ALMEIDA-CORREA, Renata CRUZ, Frederik DETHLOFF et. al.

Basic information

Original name

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

Authors

EBERT, Tim (276 Germany), Daniel E. HEINZ (276 Germany), Suellen ALMEIDA-CORREA, Renata CRUZ, Frederik DETHLOFF (276 Germany), Tibor ŠTARK (703 Slovakia, belonging to the institution), Thomas BAJAJ, Oriana M. MAUREL (380 Italy), Fabiola M. RIBEIRO, Silvio CALCAGNINI (380 Italy), Kathrin HAFNER (276 Germany), Nils C. GASSEN (276 Germany), Christoph W. TURCK (276 Germany), Benoit BOULAT, Michael CZISCH (276 Germany) and Carsten T. WOTJAK (276 Germany, guarantor)

Edition

frontiers in aging neuroscience, LAUSANNE, FRONTIERS MEDIA SA, 2021, 1663-4365

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30104 Pharmacology and pharmacy

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 5.702

RIV identification code

RIV/00216224:14110/21:00122834

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.3389/fnagi.2021.731603

UT WoS

000726118100001

Keywords in English

spatial memory; biomarker; MRS; MCI; gliaastrocytes; microgliamyo-inositol

Abstract

V originále

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.

Links

MUNI/A/1249/2020, interní kód MU

Name: Základní výzkum v oblasti farmakokinetiky, neurobiologie závislostí a aplikovaný výzkum v oblasti personalizované farmakoterapie v onkologii (Acronym: SV_Farmakologie2021)

Investor: Masaryk University

Citovat

EBERT, Tim, Daniel E. HEINZ, Suellen ALMEIDA-CORREA, Renata CRUZ, Frederik DETHLOFF, Tibor ŠTARK, Thomas BAJAJ, Oriana M. MAUREL, Fabiola M. RIBEIRO, Silvio CALCAGNINI, Kathrin HAFNER, Nils C. GASSEN, Christoph W. TURCK, Benoit BOULAT, Michael CZISCH and 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. LAUSANNE: FRONTIERS MEDIA SA, 2021, vol. 13, November 2021, p. 1-17. ISSN 1663-4365. Available from: https://dx.doi.org/10.3389/fnagi.2021.731603.

@article{1803343,
   author = {Ebert, Tim and Heinz, Daniel E. and AlmeidaandCorrea, Suellen and Cruz, Renata and Dethloff, Frederik and Štark, Tibor and Bajaj, Thomas and Maurel, Oriana M. and Ribeiro, Fabiola M. and Calcagnini, Silvio and Hafner, Kathrin and Gassen, Nils C. and Turck, Christoph W. and Boulat, Benoit and Czisch, Michael and Wotjak, Carsten T.},
   article_location = {LAUSANNE},
   article_number = {November 2021},
   doi = {http://dx.doi.org/10.3389/fnagi.2021.731603},
   keywords = {spatial memory; biomarker; MRS; MCI; gliaastrocytes; microgliamyo-inositol},
   language = {eng},
   issn = {1663-4365},
   journal = {frontiers in aging neuroscience},
   title = {Myo-Inositol Levels in the Dorsal Hippocampus Serve as Glial Prognostic Marker of Mild Cognitive Impairment in Mice},
   url = {https://www.frontiersin.org/articles/10.3389/fnagi.2021.731603/full},
   volume = {13},
   year = {2021}
}

TY  - JOUR
ID  - 1803343
AU  - Ebert, Tim - Heinz, Daniel E. - Almeida-Correa, Suellen - Cruz, Renata - Dethloff, Frederik - Štark, Tibor - Bajaj, Thomas - Maurel, Oriana M. - Ribeiro, Fabiola M. - Calcagnini, Silvio - Hafner, Kathrin - Gassen, Nils C. - Turck, Christoph W. - Boulat, Benoit - Czisch, Michael - Wotjak, Carsten T.
PY  - 2021
TI  - Myo-Inositol Levels in the Dorsal Hippocampus Serve as Glial Prognostic Marker of Mild Cognitive Impairment in Mice
JF  - frontiers in aging neuroscience
VL  - 13
IS  - November 2021
SP  - 1-17
EP  - 1-17
PB  - FRONTIERS MEDIA SA
SN  - 16634365
KW  - spatial memory
KW  - biomarker
KW  - MRS
KW  - MCI
KW  - gliaastrocytes
KW  - microgliamyo-inositol
UR  - https://www.frontiersin.org/articles/10.3389/fnagi.2021.731603/full
N2  - 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.
ER  -

EBERT, Tim, Daniel E. HEINZ, Suellen ALMEIDA-CORREA, Renata CRUZ, Frederik DETHLOFF, Tibor ŠTARK, Thomas BAJAJ, Oriana M. MAUREL, Fabiola M. RIBEIRO, Silvio CALCAGNINI, Kathrin HAFNER, Nils C. GASSEN, Christoph W. TURCK, Benoit BOULAT, Michael CZISCH and Carsten T. WOTJAK. Myo-Inositol Levels in the Dorsal Hippocampus Serve as Glial Prognostic Marker of Mild Cognitive Impairment in Mice. \textit{frontiers in aging neuroscience}. LAUSANNE: FRONTIERS MEDIA SA, 2021, vol.~13, November 2021, p.~1-17. ISSN~1663-4365. Available from: https://dx.doi.org/10.3389/fnagi.2021.731603.

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