NDLI: Location- and Subunit-Specific NMDA Receptors Determine the Developmental Sevoflurane Neurotoxicity Through ERK1/2 Signaling

Content Provider	Springer Nature Link
Author	Wang, Wen Yuan Jia, Li Jie Luo, Yan Zhang, Hong Hai Cai, Fang Mao, Hui Xu, Wei Cai Fang, Jun Biao Peng, Zhi You Ma, Zheng Wen Chen, Yan Hong Zhang, Juan Wei, Zhen Yu, Bu Wei Hu, Shuang Fei
Copyright Year	2014
Abstract	It is well established that developmental exposure of sevoflurane (an inhalational anesthetic) is capable of inducing neuronal apoptosis and subsequent learning and memory disorders. Synaptic NMDA receptors activity plays an essential role in cell survival, while the extra-synaptic NMDA receptors activation is usually associated with cell death. However, whether synaptic or extra-synaptic NMDA receptors mediate developmental sevoflurane neurotoxicity is largely unknown. Here, we show that developmental sevoflurane treatment decreased NR2A, but increased NR2B subunit expression both in vitro and in vivo. Sevoflurane-induced neuronal apoptosis was attenuated by synaptic NMDA receptors activation or low dose of exogenous NMDA in vitro. Interestingly, these effects could be abolished by NR2A inhibitor PEAQX, but not NR2B inhibitor Ifenprodil in vitro. In contrast, activation of extra-synaptic NMDA receptors alone had no effects on sevoflurane neurotoxicity. In the scenario of extra-synaptic NMDA receptors stimulation, however, sevoflurane-induced neuronal apoptosis could be prevented by addition of Ifenprodil, but not by PEAQX in vitro. In addition, sevoflurane neurotoxicity could also be rescued by memantine, an uncompetitive antagonist for preferential blockade of extra-synaptic NMDA receptors both in vitro and in vivo. Furthermore, we found that developmental sevoflurane-induced phospho-ERK1/2 inhibition was restored by synaptic NMDA receptor activation (in vitro), low dose of NMDA (in vitro) or memantine (in vivo). And the neuroprotective role of synaptic NMDA activity was able to be reversed by MEK1/2 inhibitor U0126 in vitro. Finally, administration of memantine or NMDA significantly improved spatial learning and memory dysfunctions induced by developmental sevoflurane exposure without influence on locomotor activity. These results indicated that activation of synaptic NR2A-containing NMDA receptors, or inhibition of extra-synaptic NR2B-containing NMDA receptors contributed to the relief of sevoflurane neurotoxicity, and the ERK1/2 MAPK signaling may be involved in this process.
Starting Page	216
Ending Page	230
Page Count	15
File Format	PDF
ISSN	08937648
Journal	Molecular Neurobiology
Volume Number	53
Issue Number	1
e-ISSN	15591182
Language	English
Publisher	Springer US
Publisher Date	2014-11-25
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Sevoflurane NR2A-containing NMDA receptors NR2B-containing NMDA receptors Apoptosis ERK1/2 MAPK signaling Developing brain Neurosciences Neurobiology Cell Biology Neurology
Content Type	Text
Resource Type	Article
Subject	Neurology Cellular and Molecular Neuroscience

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Dexmedetomidine Prevents Sevoflurane Neurotoxicity via ERK1/2 MAPK Signaling in the Developing Brain

Synaptic and extrasynaptic NMDA receptors: Problems and prospects

EHMTI-0308. Cortical spreading depression increases NR2A/NR2B ratio by altering numbers of nr2a and nr2b subunit-containing nmda receptors in the hippocampus

Cellular/molecular development and subunit composition of synaptic nmda receptors in the amygdala: nr2b synapses in the adult central.

Role of NMDA receptor subtypes in different forms of NMDA-dependent synaptic plasticity

Neuroprotective Mechanisms of Lycium barbarum Polysaccharides Against Ischemic Insults by Regulating NR2B and NR2A Containing NMDA Receptor Signaling Pathways

EHMTI-0308. Cortical spreading depression increases NR2A/NR2B ratio by altering numbers of nr2a and nr2b subunit-containing nmda receptors in the hippocampus

NR2A and NR2B subunit containing NMDA receptors differentially regulate striatal output pathways

The protective effects of Achyranthes bidentata polypeptides against NMDA-induced cell apoptosis in cultured hippocampal neurons through differential modulation of NR2A- and NR2B-containing NMDA receptors

Location- and Subunit-Specific NMDA Receptors Determine the Developmental Sevoflurane Neurotoxicity Through ERK1/2 Signaling

Similar Documents

Dexmedetomidine Prevents Sevoflurane Neurotoxicity via ERK1/2 MAPK Signaling in the Developing Brain

Synaptic and extrasynaptic NMDA receptors: Problems and prospects

EHMTI-0308. Cortical spreading depression increases NR2A/NR2B ratio by altering numbers of nr2a and nr2b subunit-containing nmda receptors in the hippocampus

Cellular/molecular development and subunit composition of synaptic nmda receptors in the amygdala: nr2b synapses in the adult central.

Role of NMDA receptor subtypes in different forms of NMDA-dependent synaptic plasticity

Neuroprotective Mechanisms of Lycium barbarum Polysaccharides Against Ischemic Insults by Regulating NR2B and NR2A Containing NMDA Receptor Signaling Pathways

EHMTI-0308. Cortical spreading depression increases NR2A/NR2B ratio by altering numbers of nr2a and nr2b subunit-containing nmda receptors in the hippocampus

NR2A and NR2B subunit containing NMDA receptors differentially regulate striatal output pathways

The protective effects of Achyranthes bidentata polypeptides against NMDA-induced cell apoptosis in cultured hippocampal neurons through differential modulation of NR2A- and NR2B-containing NMDA receptors

Location- and Subunit-Specific NMDA Receptors Determine the Developmental Sevoflurane Neurotoxicity Through ERK1/2 Signaling