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Reduced brain fractalkine-CX3CR1 signaling is involved in the impaired cognition of streptozotocin-treated mice
Patients with diabetes mellitus are predisposed to cognitive impairment. Fractalkine-CX3CR1 in the brain signaling represents a primary neuron-microglia inter-regulatory system for several brain functions including learning and memory processes. The present study addressed whether fractalkine-CX3CR1...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509139/ https://www.ncbi.nlm.nih.gov/pubmed/32995659 http://dx.doi.org/10.1016/j.ibror.2020.09.002 |
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author | Kawamura, Namiko Katsuura, Goro Yamada-Goto, Nobuko Novianti, Ela Inui, Akio Asakawa, Akihiro |
author_facet | Kawamura, Namiko Katsuura, Goro Yamada-Goto, Nobuko Novianti, Ela Inui, Akio Asakawa, Akihiro |
author_sort | Kawamura, Namiko |
collection | PubMed |
description | Patients with diabetes mellitus are predisposed to cognitive impairment. Fractalkine-CX3CR1 in the brain signaling represents a primary neuron-microglia inter-regulatory system for several brain functions including learning and memory processes. The present study addressed whether fractalkine-CX3CR1 signaling in the hippocampus contributes to the cognitive deficits observed in streptozotocin (STZ)-treated mice. Our results showed that STZ-treated mice exhibited significant cognitive deficits in the Y-maze test, and a decrease in fractalkine and CX3CR1 levels in the hippocampus. Moreover, intracerebroventricular injection of the CX3CR1 antagonist 18a in normal mice induced significant cognitive deficits in the Y-maze test. STZ-treated mice showed a significant increase in plasma corticosterone levels and a decrease in plasma and hippocampal levels of insulin-like growth factor-1 (IGF-1). Therefore, we examined the effects of corticosterone and IGF-1 on regulation of fractalkine and CX3CR1 expression. Dexamethasone (DEX) application significantly decreased the mRNA expression of fractalkine in primary neuron and astrocyte cultures, and of CX3CR1 in primary microglia cultures. On the other hand, IGF-1 application significantly increased the mRNA expression of fractalkine in primary neuron cultures and CX3CR1 in primary microglia cultures. In addition, administration of DEX and the IGF-1 receptor tyrosine kinase inhibitor picropodophyllin significantly reduced the mRNA expression of fractalkine and CX3CR1 in the hippocampus. These findings indicate that impaired cognition in STZ-treated mice is associated with reduced fractalkine-CX3CR1 signaling in the hippocampus which may be induced by an increase in corticosterone and a decrease in IGF-1. |
format | Online Article Text |
id | pubmed-7509139 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-75091392020-09-28 Reduced brain fractalkine-CX3CR1 signaling is involved in the impaired cognition of streptozotocin-treated mice Kawamura, Namiko Katsuura, Goro Yamada-Goto, Nobuko Novianti, Ela Inui, Akio Asakawa, Akihiro IBRO Rep Research Paper Patients with diabetes mellitus are predisposed to cognitive impairment. Fractalkine-CX3CR1 in the brain signaling represents a primary neuron-microglia inter-regulatory system for several brain functions including learning and memory processes. The present study addressed whether fractalkine-CX3CR1 signaling in the hippocampus contributes to the cognitive deficits observed in streptozotocin (STZ)-treated mice. Our results showed that STZ-treated mice exhibited significant cognitive deficits in the Y-maze test, and a decrease in fractalkine and CX3CR1 levels in the hippocampus. Moreover, intracerebroventricular injection of the CX3CR1 antagonist 18a in normal mice induced significant cognitive deficits in the Y-maze test. STZ-treated mice showed a significant increase in plasma corticosterone levels and a decrease in plasma and hippocampal levels of insulin-like growth factor-1 (IGF-1). Therefore, we examined the effects of corticosterone and IGF-1 on regulation of fractalkine and CX3CR1 expression. Dexamethasone (DEX) application significantly decreased the mRNA expression of fractalkine in primary neuron and astrocyte cultures, and of CX3CR1 in primary microglia cultures. On the other hand, IGF-1 application significantly increased the mRNA expression of fractalkine in primary neuron cultures and CX3CR1 in primary microglia cultures. In addition, administration of DEX and the IGF-1 receptor tyrosine kinase inhibitor picropodophyllin significantly reduced the mRNA expression of fractalkine and CX3CR1 in the hippocampus. These findings indicate that impaired cognition in STZ-treated mice is associated with reduced fractalkine-CX3CR1 signaling in the hippocampus which may be induced by an increase in corticosterone and a decrease in IGF-1. Elsevier 2020-09-15 /pmc/articles/PMC7509139/ /pubmed/32995659 http://dx.doi.org/10.1016/j.ibror.2020.09.002 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Paper Kawamura, Namiko Katsuura, Goro Yamada-Goto, Nobuko Novianti, Ela Inui, Akio Asakawa, Akihiro Reduced brain fractalkine-CX3CR1 signaling is involved in the impaired cognition of streptozotocin-treated mice |
title | Reduced brain fractalkine-CX3CR1 signaling is involved in the impaired cognition of streptozotocin-treated mice |
title_full | Reduced brain fractalkine-CX3CR1 signaling is involved in the impaired cognition of streptozotocin-treated mice |
title_fullStr | Reduced brain fractalkine-CX3CR1 signaling is involved in the impaired cognition of streptozotocin-treated mice |
title_full_unstemmed | Reduced brain fractalkine-CX3CR1 signaling is involved in the impaired cognition of streptozotocin-treated mice |
title_short | Reduced brain fractalkine-CX3CR1 signaling is involved in the impaired cognition of streptozotocin-treated mice |
title_sort | reduced brain fractalkine-cx3cr1 signaling is involved in the impaired cognition of streptozotocin-treated mice |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509139/ https://www.ncbi.nlm.nih.gov/pubmed/32995659 http://dx.doi.org/10.1016/j.ibror.2020.09.002 |
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