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Title: Isoflurane induced cognitive impairment in aged rats through hippocampal calcineurin/NFAT signaling

Abstract

Calcineurin (CaN) over-activation constrains synaptic plasticity and memory formation. Upon CaN activation, NFAT imports into the nucleus and guides its downstream genes, which also affect neuronal and synaptic function. Aberrant CaN/NFAT signaling involves in neurotoxicity and cognitive impairment in neurological disorders such as Alzheimer's disease, but its role in postoperative cognitive dysfunction (POCD) remains uninvestigated. Inhaled anesthetic isoflurane facilitates the development of POCD, and the present study investigated the role of CaN/NFAT signaling in isoflurane induced cognitive impairment of aged rats, and the therapeutic effects of CaN inhibitor cyclosporine A (CsA). The results indicated that hippocampal CaN activity increased and peaked at 6 h after isoflurane exposure, and NFAT, especially NFATc4, imported into the nucleus following CaN activation. Furthermore, phamacological inhibition of CaN by CsA markedly attenuated isoflurane induced aberrant CaN/NFATc4 signaling in the hippocampus, and rescued relevant spatial learning and memory impairment of aged rats. Overall, the study suggests hippocampal CaN/NFAT signaling as the upstream mechanism of isoflurane induced cognitive impairment, and provides potential therapeutic target and possible treatment methods for POCD. - Highlights: • Isoflurane induces hippocampal calcineurin activation. • Isoflurane induces hippocampal NFAT, especially NFATc4, nuclear import. • Cyclosporine A attenuates isoflurane induced aberrant calcineurin/NFAT signaling. • Cyclosporinemore » A rescues isoflurane induced cognitive impairment. • Calcineurin/NFAT signaling is the upstream mechanism of isoflurane induced synaptic dysfunction and cognitive impairment.« less

Authors:
; ; ; ; ;
Publication Date:
OSTI Identifier:
22462046
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 460; Journal Issue: 4; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANESTHETICS; CYCLOSPORINE; DISEASES; GENES; HIPPOCAMPUS; INHIBITION; LEARNING; PLASTICITY; RATS; SIGNALS

Citation Formats

Ni, Cheng, Li, Zhengqian, Qian, Min, Zhou, Yang, Wang, Jun, and Guo, Xiangyang, E-mail: puthmzk@163.com. Isoflurane induced cognitive impairment in aged rats through hippocampal calcineurin/NFAT signaling. United States: N. p., 2015. Web. doi:10.1016/J.BBRC.2015.03.083.
Ni, Cheng, Li, Zhengqian, Qian, Min, Zhou, Yang, Wang, Jun, & Guo, Xiangyang, E-mail: puthmzk@163.com. Isoflurane induced cognitive impairment in aged rats through hippocampal calcineurin/NFAT signaling. United States. doi:10.1016/J.BBRC.2015.03.083.
Ni, Cheng, Li, Zhengqian, Qian, Min, Zhou, Yang, Wang, Jun, and Guo, Xiangyang, E-mail: puthmzk@163.com. Fri . "Isoflurane induced cognitive impairment in aged rats through hippocampal calcineurin/NFAT signaling". United States. doi:10.1016/J.BBRC.2015.03.083.
@article{osti_22462046,
title = {Isoflurane induced cognitive impairment in aged rats through hippocampal calcineurin/NFAT signaling},
author = {Ni, Cheng and Li, Zhengqian and Qian, Min and Zhou, Yang and Wang, Jun and Guo, Xiangyang, E-mail: puthmzk@163.com},
abstractNote = {Calcineurin (CaN) over-activation constrains synaptic plasticity and memory formation. Upon CaN activation, NFAT imports into the nucleus and guides its downstream genes, which also affect neuronal and synaptic function. Aberrant CaN/NFAT signaling involves in neurotoxicity and cognitive impairment in neurological disorders such as Alzheimer's disease, but its role in postoperative cognitive dysfunction (POCD) remains uninvestigated. Inhaled anesthetic isoflurane facilitates the development of POCD, and the present study investigated the role of CaN/NFAT signaling in isoflurane induced cognitive impairment of aged rats, and the therapeutic effects of CaN inhibitor cyclosporine A (CsA). The results indicated that hippocampal CaN activity increased and peaked at 6 h after isoflurane exposure, and NFAT, especially NFATc4, imported into the nucleus following CaN activation. Furthermore, phamacological inhibition of CaN by CsA markedly attenuated isoflurane induced aberrant CaN/NFATc4 signaling in the hippocampus, and rescued relevant spatial learning and memory impairment of aged rats. Overall, the study suggests hippocampal CaN/NFAT signaling as the upstream mechanism of isoflurane induced cognitive impairment, and provides potential therapeutic target and possible treatment methods for POCD. - Highlights: • Isoflurane induces hippocampal calcineurin activation. • Isoflurane induces hippocampal NFAT, especially NFATc4, nuclear import. • Cyclosporine A attenuates isoflurane induced aberrant calcineurin/NFAT signaling. • Cyclosporine A rescues isoflurane induced cognitive impairment. • Calcineurin/NFAT signaling is the upstream mechanism of isoflurane induced synaptic dysfunction and cognitive impairment.},
doi = {10.1016/J.BBRC.2015.03.083},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 4,
volume = 460,
place = {United States},
year = {2015},
month = {5}
}