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Age-Related Decrease in Glucagon-Like Peptide-1 in Mouse Prefrontal Cortex but Not in Hippocampus Despite the Preservation of Its Receptor

Received: 5 January 2015     Accepted: 20 January 2015     Published: 30 January 2015
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Abstract

Glucagon-like peptide-1 receptor (GLP-1R) agonist treatment has the potential to be a novel therapeutic treatment for Alzheimer’s disease (AD). We previously reported that exendin-4, a Gαs protein-coupled GLP-1R agonist, up-regulates the membrane AMPA receptor GluR1 subunit in the neocortex. However, it is uncertain whether GLP-1R agonists have an advantage as an AD treatment target compared with other Gαs protein-coupled receptors. Here we show that both the protein level of proglucagon, a precursor of GLP-1, and the immunoreactivity level of GLP-1 are significantly decreased in the medial prefrontal cortex (mPFC) of aged mice (14 months old) compared with young (3 weeks old) or adult (6 months old) mice, but not in area CA1, the dentate gyrus (DG) nor in the nucleus of the solitary tract. However, the protein and immunoreactivity levels of GLP-1R in the mPFC, DG and hippocampal CA1 and CA3 areas were preserved in the aged mice. We then confirmed whether the age-dependent decrease in GLP-1 in the mPFC was associated with the activity level or the number of microglial cells in the mPFC. Co-staining of CD11b and GLP-1 in the mPFC revealed that the number of CD11b-positive cells was increased in the aged mice. Moreover, lipopolysaccharide (LPS) injection increased the number of CD11b-positive cells in the mPFC, but the number of GLP-1-positive cells was unchanged. However, the number of CD11b-positive cells that co-localized with GLP-1R in the mPFC is increased by LPS and aging. Because the GLP-1R is preserved in aged mPFC, but the amount of GLP-1 produced in the brain region is diminished, and spatial cognitive memory was impaired in aged mice, we propose that treatment with GLP-1 analogues has great promise for rescuing and ameliorating the age-related mPFC-dependent decline of cognitive functions.

Published in American Journal of BioScience (Volume 3, Issue 1)
DOI 10.11648/j.ajbio.20150301.13
Page(s) 11-27
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2015. Published by Science Publishing Group

Keywords

Glucagon-Like Peptide-1, Age-Related, Medial Prefrontal Cortex, Microglia, Alzheimer's Disease

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    Ryo Ohshima, Kanae Hotsumi, Christian Holscher, Kenjiro Seki. (2015). Age-Related Decrease in Glucagon-Like Peptide-1 in Mouse Prefrontal Cortex but Not in Hippocampus Despite the Preservation of Its Receptor. American Journal of BioScience, 3(1), 11-27. https://doi.org/10.11648/j.ajbio.20150301.13

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    ACS Style

    Ryo Ohshima; Kanae Hotsumi; Christian Holscher; Kenjiro Seki. Age-Related Decrease in Glucagon-Like Peptide-1 in Mouse Prefrontal Cortex but Not in Hippocampus Despite the Preservation of Its Receptor. Am. J. BioScience 2015, 3(1), 11-27. doi: 10.11648/j.ajbio.20150301.13

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    AMA Style

    Ryo Ohshima, Kanae Hotsumi, Christian Holscher, Kenjiro Seki. Age-Related Decrease in Glucagon-Like Peptide-1 in Mouse Prefrontal Cortex but Not in Hippocampus Despite the Preservation of Its Receptor. Am J BioScience. 2015;3(1):11-27. doi: 10.11648/j.ajbio.20150301.13

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  • @article{10.11648/j.ajbio.20150301.13,
      author = {Ryo Ohshima and Kanae Hotsumi and Christian Holscher and Kenjiro Seki},
      title = {Age-Related Decrease in Glucagon-Like Peptide-1 in Mouse Prefrontal Cortex but Not in Hippocampus Despite the Preservation of Its Receptor},
      journal = {American Journal of BioScience},
      volume = {3},
      number = {1},
      pages = {11-27},
      doi = {10.11648/j.ajbio.20150301.13},
      url = {https://doi.org/10.11648/j.ajbio.20150301.13},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajbio.20150301.13},
      abstract = {Glucagon-like peptide-1 receptor (GLP-1R) agonist treatment has the potential to be a novel therapeutic treatment for Alzheimer’s disease (AD). We previously reported that exendin-4, a Gαs protein-coupled GLP-1R agonist, up-regulates the membrane AMPA receptor GluR1 subunit in the neocortex. However, it is uncertain whether GLP-1R agonists have an advantage as an AD treatment target compared with other Gαs protein-coupled receptors. Here we show that both the protein level of proglucagon, a precursor of GLP-1, and the immunoreactivity level of GLP-1 are significantly decreased in the medial prefrontal cortex (mPFC) of aged mice (14 months old) compared with young (3 weeks old) or adult (6 months old) mice, but not in area CA1, the dentate gyrus (DG) nor in the nucleus of the solitary tract. However, the protein and immunoreactivity levels of GLP-1R in the mPFC, DG and hippocampal CA1 and CA3 areas were preserved in the aged mice. We then confirmed whether the age-dependent decrease in GLP-1 in the mPFC was associated with the activity level or the number of microglial cells in the mPFC. Co-staining of CD11b and GLP-1 in the mPFC revealed that the number of CD11b-positive cells was increased in the aged mice. Moreover, lipopolysaccharide (LPS) injection increased the number of CD11b-positive cells in the mPFC, but the number of GLP-1-positive cells was unchanged. However, the number of CD11b-positive cells that co-localized with GLP-1R in the mPFC is increased by LPS and aging. Because the GLP-1R is preserved in aged mPFC, but the amount of GLP-1 produced in the brain region is diminished, and spatial cognitive memory was impaired in aged mice, we propose that treatment with GLP-1 analogues has great promise for rescuing and ameliorating the age-related mPFC-dependent decline of cognitive functions.},
     year = {2015}
    }
    

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  • TY  - JOUR
    T1  - Age-Related Decrease in Glucagon-Like Peptide-1 in Mouse Prefrontal Cortex but Not in Hippocampus Despite the Preservation of Its Receptor
    AU  - Ryo Ohshima
    AU  - Kanae Hotsumi
    AU  - Christian Holscher
    AU  - Kenjiro Seki
    Y1  - 2015/01/30
    PY  - 2015
    N1  - https://doi.org/10.11648/j.ajbio.20150301.13
    DO  - 10.11648/j.ajbio.20150301.13
    T2  - American Journal of BioScience
    JF  - American Journal of BioScience
    JO  - American Journal of BioScience
    SP  - 11
    EP  - 27
    PB  - Science Publishing Group
    SN  - 2330-0167
    UR  - https://doi.org/10.11648/j.ajbio.20150301.13
    AB  - Glucagon-like peptide-1 receptor (GLP-1R) agonist treatment has the potential to be a novel therapeutic treatment for Alzheimer’s disease (AD). We previously reported that exendin-4, a Gαs protein-coupled GLP-1R agonist, up-regulates the membrane AMPA receptor GluR1 subunit in the neocortex. However, it is uncertain whether GLP-1R agonists have an advantage as an AD treatment target compared with other Gαs protein-coupled receptors. Here we show that both the protein level of proglucagon, a precursor of GLP-1, and the immunoreactivity level of GLP-1 are significantly decreased in the medial prefrontal cortex (mPFC) of aged mice (14 months old) compared with young (3 weeks old) or adult (6 months old) mice, but not in area CA1, the dentate gyrus (DG) nor in the nucleus of the solitary tract. However, the protein and immunoreactivity levels of GLP-1R in the mPFC, DG and hippocampal CA1 and CA3 areas were preserved in the aged mice. We then confirmed whether the age-dependent decrease in GLP-1 in the mPFC was associated with the activity level or the number of microglial cells in the mPFC. Co-staining of CD11b and GLP-1 in the mPFC revealed that the number of CD11b-positive cells was increased in the aged mice. Moreover, lipopolysaccharide (LPS) injection increased the number of CD11b-positive cells in the mPFC, but the number of GLP-1-positive cells was unchanged. However, the number of CD11b-positive cells that co-localized with GLP-1R in the mPFC is increased by LPS and aging. Because the GLP-1R is preserved in aged mPFC, but the amount of GLP-1 produced in the brain region is diminished, and spatial cognitive memory was impaired in aged mice, we propose that treatment with GLP-1 analogues has great promise for rescuing and ameliorating the age-related mPFC-dependent decline of cognitive functions.
    VL  - 3
    IS  - 1
    ER  - 

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Author Information
  • Department of Pharmacology, School of Pharmaceutical Science, Ohu University, 31-1 Misumido, Tomitamachi, Koriyama, Fukushima, Japan

  • Department of Pharmacology, School of Pharmaceutical Science, Ohu University, 31-1 Misumido, Tomitamachi, Koriyama, Fukushima, Japan

  • Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, UK

  • Department of Pharmacology, School of Pharmaceutical Science, Ohu University, 31-1 Misumido, Tomitamachi, Koriyama, Fukushima, Japan

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