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

Ryo Ohshima; Kanae Hotsumi; Christian Holscher; Kenjiro Seki

doi:doi:10.11648/j.ajbio.20150301.13

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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

Ryo Ohshima, Kanae Hotsumi, Christian Holscher, Kenjiro Seki

Published in American Journal of BioScience (Volume 3, Issue 1)

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

References

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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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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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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

Ryo Ohshima

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

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

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

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

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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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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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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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