PMID- 33465356
OWN - NLM
STAT- MEDLINE
DCOM- 20210519
LR  - 20240226
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 895
DP  - 2021 Mar 15
TI  - GR/NF-kappaB signaling pathway regulates hippocampal inflammatory responses in 
      diabetic rats with chronic unpredictable mild stress.
PG  - 173861
LID - S0014-2999(21)00014-5 [pii]
LID - 10.1016/j.ejphar.2021.173861 [doi]
AB  - Clinical studies have shown that diabetes can present with underlying depression, 
      and a combination of the two can lead to emotional, memory and cognitive 
      disorders, closely associated with hippocampal neuroinflammation. However, the 
      mechanism underlying the development of hippocampal neuroinflammation under the 
      above condition remains elusive. The aims of this study were to explore the 
      pathogenesis of diabetes combined with depression, and the effect of 
      dexamethasone (Dex), a glucocorticoid receptor (GR) agonist, on hippocampal 
      neuroinflammation in diabetic rats with chronic unpredictable mild stress (CUMS). 
      Therefore, rats were intragastrically fed on a high-fat diet (10% cholesterol 
      10 ml/kg) for 14 days and thereafter injected with 38 mg/kg of streptozotocin on 
      the 15th day to induce diabetes. Dex treatment of the diabetic and CUMS rats 
      ameliorated the depression-associated behavior in the respective rats. Apart from 
      enhanced depressive behavior, diabetes-depressed condition also up-regulated the 
      expression of hippocampus microglia chemokine Ⅰ receptor (CX3CR1) and secretion 
      of several pro-inflammatory factors, in particular, interleukin 1beta (IL-1beta), 
      interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor - alpha (TNF-alpha). 
      Hematoxylin-eosin staining revealed inflammatory damages in the hippocampus. 
      Western blot analysis further revealed repression of GR proteins converse to the 
      nuclear factor kappa-B (NF-kappaB) proteins, which were up-regulated. Intriguingly, 
      Dex reversed the above events by inhibiting inflammatory reactions in the 
      hippocampus. Consequently, played an antidepressant effect in diabetic and CUMS 
      model rats. Overall, findings of this research suggest that the physiopathology 
      of diabetes with stress cormobity are mediated by inflammatory reactions in the 
      hippocampus. In particular, the responses are associated with regulation of 
      GR/NF-kappaB signaling pathway.
CI  - Copyright (c) 2021 Elsevier B.V. All rights reserved.
FAU - Li, Zi-Rong
AU  - Li ZR
AD  - State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan 
      (incubation), Hunan University of Chinese Medicine, Changsha, Hunan, China.
FAU - Han, Yuan-Shan
AU  - Han YS
AD  - Department of Experimental Center for Medical Innovation, The First Affiliated 
      Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China.
FAU - Liu, Zhuo
AU  - Liu Z
AD  - Department of Education and Science, Affiliated Hospital of Hunan Academy of 
      Traditional Chinese Medicine, Changsha, China. Electronic address: 
      330811844@qq.com.
FAU - Zhao, Hong-Qing
AU  - Zhao HQ
AD  - State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan 
      (incubation), Hunan University of Chinese Medicine, Changsha, Hunan, China.
FAU - Liu, Jian
AU  - Liu J
AD  - Department of Experimental Center for Medical Innovation, The First Affiliated 
      Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China.
FAU - Yang, Hui
AU  - Yang H
AD  - Department of Experimental Center for Medical Innovation, The First Affiliated 
      Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China.
FAU - Wang, Yu-Hong
AU  - Wang YH
AD  - State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan 
      (incubation), Hunan University of Chinese Medicine, Changsha, Hunan, China. 
      Electronic address: wyhyjy620@126.com.
LA  - eng
PT  - Journal Article
DEP - 20210116
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Antidepressive Agents)
RN  - 0 (Blood Glucose)
RN  - 0 (Cytokines)
RN  - 0 (Glucocorticoids)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Lipids)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 7S5I7G3JQL (Dexamethasone)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/pharmacology
MH  - Behavior, Animal
MH  - Blood Glucose/metabolism
MH  - Chronic Disease
MH  - Cytokines/metabolism
MH  - Depression/*metabolism/physiopathology/prevention & control/psychology
MH  - Dexamethasone/pharmacology
MH  - Diabetes Mellitus, Experimental/drug therapy/*metabolism/physiopathology
MH  - Glucocorticoids/pharmacology
MH  - Hippocampus/drug effects/*metabolism/physiopathology
MH  - Inflammation/*metabolism/physiopathology/prevention & control/psychology
MH  - Inflammation Mediators/*metabolism
MH  - Lipids/blood
MH  - Morris Water Maze Test
MH  - NF-kappa B/*metabolism
MH  - Open Field Test
MH  - Rats, Sprague-Dawley
MH  - Receptors, Glucocorticoid/agonists/*metabolism
MH  - Signal Transduction
MH  - Stress, Psychological/drug therapy/*metabolism/physiopathology/psychology
MH  - Rats
OTO - NOTNLM
OT  - Chronic unpredictable mild stress
OT  - Diabetic model rats
OT  - GR
OT  - Hippocampal
OT  - Inflammatory
OT  - NF-kappaB signaling pathway
EDAT- 2021/01/20 06:00
MHDA- 2021/05/20 06:00
CRDT- 2021/01/19 20:08
PHST- 2020/06/14 00:00 [received]
PHST- 2020/12/23 00:00 [revised]
PHST- 2021/01/07 00:00 [accepted]
PHST- 2021/01/20 06:00 [pubmed]
PHST- 2021/05/20 06:00 [medline]
PHST- 2021/01/19 20:08 [entrez]
AID - S0014-2999(21)00014-5 [pii]
AID - 10.1016/j.ejphar.2021.173861 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2021 Mar 15;895:173861. doi: 10.1016/j.ejphar.2021.173861. Epub 
      2021 Jan 16.