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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...

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Autores principales: Kawamura, Namiko, Katsuura, Goro, Yamada-Goto, Nobuko, Novianti, Ela, Inui, Akio, Asakawa, Akihiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
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.
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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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