PMID- 35831873
OWN - NLM
STAT- MEDLINE
DCOM- 20220715
LR  - 20220716
IS  - 1742-2094 (Electronic)
IS  - 1742-2094 (Linking)
VI  - 19
IP  - 1
DP  - 2022 Jul 13
TI  - Transient neuroinflammation following surgery contributes to long-lasting 
      cognitive decline in elderly rats via dysfunction of synaptic NMDA receptor.
PG  - 181
LID - 10.1186/s12974-022-02528-5 [doi]
LID - 181
AB  - BACKGROUND: Perioperative neurocognitive disorders (PNDs) are considered the most 
      common postoperative complication in geriatric patients. However, its 
      pathogenesis is not fully understood. Surgery-triggered neuroinflammation is a 
      major contributor to the development of PNDs. Neuroinflammation can influence 
      N-methyl-D-aspartate receptor (NMDAR) expression or function which is closely 
      associated with cognition. We, therefore, hypothesized that the persistent 
      changes in NMDAR expression or function induced by transient neuroinflammation 
      after surgery were involved in the development of PNDs. METHODS: 
      Eighteen-month-old male Sprague-Dawley rats were subjected to abdominal surgery 
      with sevoflurane anesthesia to establish the PNDs animal model. Then, we 
      determined the transient neuroinflammation by detecting the protein levels of 
      proinflammatory cytokines and microglia activation using ELISA, western blot, 
      immunohistochemistry, and microglial morphological analysis from postoperative 
      days 1-20. Persistent changes in NMDAR expression were determined by detecting 
      the protein levels of NMDAR subunits from postoperative days 1-59. Subsequently, 
      the dysfunction of synaptic NMDAR was evaluated by detecting the structural 
      plasticity of dendritic spine using Golgi staining. Pull-down assay and western 
      blot were used to detect the protein levels of Rac1-GTP, phosphor-cofilin, and 
      Arp3, which contribute to the regulation of the structural plasticity of 
      dendritic spine. Finally, glycyrrhizin, an anti-inflammatory agent, was 
      administered to further explore the role of synaptic NMDAR dysfunction induced by 
      transient neuroinflammation in the neuropathogenesis of PNDs. RESULTS: We showed 
      that transient neuroinflammation induced by surgery caused sustained 
      downregulation of synaptic NR2A and NR2B subunits in the dorsal hippocampus and 
      led to a selective long-term spatial memory deficit. Meanwhile, the detrimental 
      effect of neuroinflammation on the function of synaptic NMDARs was shown by the 
      impaired structural plasticity of dendritic spines and decreased activity of the 
      Rac1 signaling pathways during learning. Furthermore, anti-inflammatory treatment 
      reversed the downregulation and hypofunction of synaptic NR2A and NR2B and 
      subsequently rescued the long-term spatial memory deficit. CONCLUSIONS: Our 
      results identify sustained synaptic NR2A and NR2B downregulation and hypofunction 
      induced by transient neuroinflammation following surgery as important 
      contributors to the development of PNDs in elderly rats.
CI  - (c) 2022. The Author(s).
FAU - Chen, Bo
AU  - Chen B
AD  - Department of Anesthesiology, Chongqing University Cancer Hospital, Chongqing, 
      400030, People's Republic of China.
FAU - Qin, Guangcheng
AU  - Qin G
AD  - Laboratory Research Center, the First Affiliated Hospital of Chongqing Medical 
      University, Chongqing, 400016, People's Republic of China.
FAU - Xiao, Jingyu
AU  - Xiao J
AD  - Department of Anesthesiology, Chongqing University Cancer Hospital, Chongqing, 
      400030, People's Republic of China.
FAU - Deng, Xiaoyuan
AU  - Deng X
AD  - Department of Anesthesiology, Chongqing University Cancer Hospital, Chongqing, 
      400030, People's Republic of China.
FAU - Lin, Aolei
AU  - Lin A
AD  - Department of Neurology, the First Affiliated Hospital of Chongqing Medical 
      University, Chongqing, 400016, People's Republic of China.
FAU - Liu, Hongliang
AU  - Liu H
AD  - Department of Anesthesiology, Chongqing University Cancer Hospital, Chongqing, 
      400030, People's Republic of China. light3748@sina.com.
LA  - eng
GR  - cstc2019jcyj-msxmX0608/National Science Foundation Project of Chongqing/
GR  - cstc2017jcyjBX0043/National Science Foundation Project of Chongqing/
GR  - NSFC82101282/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20220713
PL  - England
TA  - J Neuroinflammation
JT  - Journal of neuroinflammation
JID - 101222974
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
SB  - IM
MH  - Animals
MH  - *Cognitive Dysfunction
MH  - Hippocampus/metabolism
MH  - Male
MH  - Memory Disorders
MH  - Neuroinflammatory Diseases
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - *Receptors, N-Methyl-D-Aspartate/metabolism
PMC - PMC9281167
OTO - NOTNLM
OT  - NMDAR
OT  - Neuroinflammation
OT  - Postoperative cognitive dysfunction
OT  - Rac1
OT  - structural plasticity
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest. The authors declare that they have no competing interests.
EDAT- 2022/07/14 06:00
MHDA- 2022/07/16 06:00
PMCR- 2022/07/13
CRDT- 2022/07/13 23:51
PHST- 2022/01/29 00:00 [received]
PHST- 2022/06/12 00:00 [accepted]
PHST- 2022/07/13 23:51 [entrez]
PHST- 2022/07/14 06:00 [pubmed]
PHST- 2022/07/16 06:00 [medline]
PHST- 2022/07/13 00:00 [pmc-release]
AID - 10.1186/s12974-022-02528-5 [pii]
AID - 2528 [pii]
AID - 10.1186/s12974-022-02528-5 [doi]
PST - epublish
SO  - J Neuroinflammation. 2022 Jul 13;19(1):181. doi: 10.1186/s12974-022-02528-5.